Risk Factors of Clostridium Difficile Infection in Hematopoietic Stem Cell Transplant Recipients: A Systemic Review and Meta-Analysis

Abstract Introduction: C. difficile infection (CDI) is a common nosocomial infection. Immune suppression is thought to be a major risk factor for CDI. Hematopoietic stem cell transplant (HSCT) recipients represent a major subgroup of immunologically vulnerable patients. It is unclear if these patients have novel risk factors for CDI development. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of CDI in HSCT recipients. Methods: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 up to June 2018. All studies that assessed risk factors associated with CDI development in HSCT recipients were eligible for inclusion. Data on clinical characteristics and risk factors associated with CDI development were collected. Study quality was assessed using the Newcastle-Ottawa scale. Meta-analyses were performed using random effects models and pooled odds ratios with 95% confidence interval (CI) for risk factors reported in ≥ 2 studies were calculated. Results: Overall, 17 studies, including 6328 HSCT patients were included. Of those 874 patients developed CDI. The rate of CDI development in these patients was 13.81% with a follow up ranging from 1- 36 months. A total of 34 different risk factors were studied, of which 20 were identified in ≥ 2 studies. Our analysis showed that cephalosporin use (Odds ratio [OR] 2.21, 95% confidence interval [CI] 1.26-3.87), cord blood transplant (OR 1.36, 95% CI 1.01-1.83), graft versus host disease (GVHD) (OR 1.63, 95% CI 1.07-2.48) & prior hospitalization within 90 days of HSCT (OR 1.85, 95% CI 1.21-2.83) were associated with statistically significant increased risk of CDI in HSCT patients (Figure 1). On the other hand, many characteristics of HSCT patients including age, diabetes, lung disease, fluoroquinolones, proton pump inhibitors, rituximab, mucositis, myeloablative therapy, melphalan use before BMT, total body irradiation, growth factor use during admission, neutropenia, autologous vs allogenic transplant and use of matched related donor were not associated with increased risk of CDI. Conclusion: HSCT recipients are at an increased risk of CDI compared to general population. In addition to the common risk factors like cephalosporin use and prior hospitalization, these patients have novel characteristics including presence of GVHD and cord blood transplant that puts them at a higher risk of CDI. HSCT patients with these risk factors may warrant a closer surveillance for early detection and treatment of CDI. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Thrombotic Microangiopathy with Tacrolimus/Sirolimus-Based GVHD Prophylaxis Regimen in Patients Undergoing Hematopoietic Stem Cell Transplant from a Matched Unrelated Donor

Blood ◽

10.1182/blood.v112.11.797.797 ◽

2008 ◽

Vol 112 (11) ◽

pp. 797-797 ◽

Cited By ~ 1

Author(s):

Tam Khuu ◽

Sepideh Shayani ◽

Joycelynne Palmer ◽

Roberto Rodriguez ◽

Pablo Miguel Parker ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Thrombotic Microangiopathy ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Gvhd Prophylaxis ◽

Increased Risk

Abstract Thrombotic microangiopathy (TMA) is a multifactorial complication of related and unrelated allogeneic hematopoietic stem cell transplant (allo-HSCT). The true incidence of TMA is difficult to estimate due to lack of agreement on a single definition. Diagnosis is often complicated by multiple potential etiologies for the clinical findings. Sirolimus (SIR), an inhibitor of mammalian target of Rapamycin (mTOR), is a novel immunosuppressive agent that works synergistically with calcineurin inhibitors (CNI) to prevent graft-versus-host disease (GVHD) in allo-HSCT. Recently, the addition of SIR to CNIs was reported to result in a higher than expected incidence (10.8%) of TMA (Cutler et al. BBMT2005; 11:551–7). We evaluated the incidence and risk factors for TMA in a cohort of patients undergoing matched unrelated (MUD) HSCT using SIR combined with tacrolimus (TAC) and mini-methotrexate for GVHD prophylaxis at City of Hope. TMA was defined as SCr increase of ≥ 50% above baseline, LDH twice the institutional upper normal limit, presence of schistocytes or persistent presence of nucleated red blood cells, and prolonged or progressive thrombocytopenia (platelets <50 × 109/L or ≥ 50% decrease from previous count). A case series of 47 MUD-HSCT patients were included in this retrospective chart review study. The median age was 50 years (range: 19–67); (male/female: 28/19). Conditioning regimens consisted of fludarabine/melphalan (65%) and FTBI combined with cyclophosphamide or etoposide (35%). Diagnoses included ALL (32%), AML (25%), NHL (15%), MDS (15%), MPD (9%), CML (2%), CLL (2%). Twenty-six patients (55%) had a 10/10 matched (HLA-A, B, C, DRB1, and DQB1) donor by high-resolution on typing. The median follow up for the 30 surviving patients is 14.5 months (2.8–26). The one-year probabilities of overall survival and non-relapse mortality (NRM) were 61% and 19%, respectively. Grade II-IV acute GVHD (aGVHD) was reported in 60% of all patients (grade III-IV: 25%). Thirteen (28%) patients met the above diagnostic criteria for TMA. In addition, we included two patients who did not meet the criteria due to missing tests but were clinically diagnosed with TMA by independent attending physicians, resulting in the total incidence of 32% (15/47). Four of the 15 patients met the criteria for TMA as a result of ongoing multi-organ failure secondary to other causes. The median time to TMA onset was five weeks (2–20 weeks). Most cases (93%) occurred within the first 100 days post-HSCT. Thirteen patients developed both TMA and aGVHD, in which the majority of patients (70%) developed TMA after a diagnosis of aGVHD had been made. Initial treatments for TMA included holding TAC (33%), holding SIR (20%), holding or adjusting doses (27% and 20%, respectively) for both drugs. One patient underwent plasma exchange. Sixty percent of patients subsequently recovered from TMA as defined by normalization of laboratory values. Of the 17 expired patients, ten were diagnosed with TMA. Causes of death were as follows: for TMA cases, relapse mortality=3, NRM=7; for Non-TMA patients, relapse mortality=6, NRM=1. At the time of TMA diagnosis, the median TAC and SIR levels were 11.3 (0–18.8) and 7 (0–23.9) ng/ml, respectively, in contrast to the median TAC and SIR levels for non-TMA patients at 6.1 (p= 0.02) and 5.5 (p=0.13) ng/ml, respectively. To identify other possible risk factors for TMA, the following patient and treatment-related characteristics were examined: age, conditioning regimen, disease type, degree of HLA match, and exposure to triazole antifungals. Only higher tacrolimus levels (HR: 6.9, p<0.01) and aGVHD grades III-IV (HR: 3.5, p=0.02) were associated with an increased risk for TMA. In conclusion, TMA is common after MUD allo-HSCT using SIR-containing GVHD prophylaxis. The risk factors for TMA suggest that careful monitoring and adjustment of TAC/SIR dosages to avoid super-therapeutic levels is critical, particularly during ongoing GVHD.

Download Full-text

Unrelated donor umbilical cord blood transplant versus unrelated hematopoietic stem cell transplant in patients with acute leukemia: A meta-analysis and systematic review

Blood Reviews ◽

10.1016/j.blre.2017.11.003 ◽

2018 ◽

Vol 32 (3) ◽

pp. 192-202 ◽

Cited By ~ 1

Author(s):

Xiao Lou ◽

Chuanhua Zhao ◽

Hu Chen

Keyword(s):

Systematic Review ◽

Stem Cell ◽

Acute Leukemia ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Meta Analysis ◽

Unrelated Donor ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Cord Blood Transplant

Download Full-text

Risk factors and epidemiology ofClostridium difficileinfection in hematopoietic stem cell transplant recipients during the peritransplant period

Transplant Infectious Disease ◽

10.1111/tid.12649 ◽

2017 ◽

Vol 19 (1) ◽

pp. e12649 ◽

Cited By ~ 4

Author(s):

Sol del Mar Aldrete ◽

Colleen S. Kraft ◽

Matthew J. Magee ◽

Austin Chan ◽

Don Hutcherson ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Transplant Recipients ◽

Hematopoietic Stem

Download Full-text

Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors

Blood ◽

10.1182/blood-2002-05-1496 ◽

2002 ◽

Vol 100 (13) ◽

pp. 4358-4366 ◽

Cited By ~ 668

Author(s):

Kieren A. Marr ◽

Rachel A. Carter ◽

Michael Boeckh ◽

Paul Martin ◽

Lawrence Corey

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Invasive Aspergillosis ◽

Respiratory Virus ◽

Stem Cell Transplant ◽

Myelogenous Leukemia ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Increased Risk ◽

Cmv Disease

The incidence of postengraftment invasive aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) recipients increased during the 1990s. We determined risks for IA and outcomes among 1682 patients who received HSCTs between January 1993 and December 1998. Risk factors included host variables (age, underlying disease), transplant variables (stem cell source), and late complications (acute and chronic graft-versus-host disease [GVHD], receipt of corticosteroids, secondary neutropenia, cytomegalovirus [CMV] disease, and respiratory virus infection). We identified risk factors associated with IA early after transplantation (≤ 40 days) and after engraftment (41-180 days). Older patient age was associated with an increased risk during both periods. Chronic myelogenous leukemia (CML) in chronic phase was associated with low risk for early IA compared with other hematologic malignancies, aplastic anemia, and myelodysplastic syndrome. Multiple myeloma was associated with an increased risk for postengraftment IA. Use of human leukocyte antigen (HLA)–matched related (MR) peripheral blood stem cells conferred protection against early IA compared with use of MR bone marrow, but use of cord blood increased the risk of IA early after transplantation. Factors that increased risks for IA after engraftment included receipt of T cell–depleted or CD34-selected stem cell products, receipt of corticosteroids, neutropenia, lymphopenia, GVHD, CMV disease, and respiratory virus infections. Very late IA (> 6 months after transplantation) was associated with chronic GVHD and CMV disease. These results emphasize the postengraftment timing of IA; risk factor analyses verify previously recognized risk factors (GVHD, receipt of corticosteroids, and neutropenia) and uncover the roles of lymphopenia and viral infections in increasing the incidence of postengraftment IA in the 1990s.

Download Full-text

Risk Factors for Falls with Injury for Patients Admitted for Hematopoietic Stem Cell Transplant

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2013.12.326 ◽

2014 ◽

Vol 20 (2) ◽

pp. S197

Author(s):

Anne M. McDonnell ◽

Brett Glotzbecker ◽

Robert J. Soiffer ◽

Joseph H. Antin ◽

Edwin P. Alyea ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Risk Factors For Falls

Download Full-text

Clinical Characteristics and Outcomes of Breakthrough Candidemia in 71 Hematologic Malignancy Patients and/or Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-center Retrospective Study From China, 2011–2018

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1523 ◽

2020 ◽

Vol 71 (Supplement_4) ◽

pp. S394-S399

Author(s):

Xiao-Chen Chen ◽

Jie Xu ◽

De-Pei Wu

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Single Center ◽

Allogeneic Transplant ◽

Hematopoietic Stem ◽

Incidence And Mortality

Abstract Background Antifungal prophylaxis may result in breakthrough infections in hematology patients with severe agranulocytosis, with few studies assessing risk factors and clinical outcomes of breakthrough candidemia. We described the distribution of Candida species, assessed risk factors for mortality in such patients, and determined differences in the incidence and mortality of breakthrough candidemia between patients who did or did not receive an allogeneic hematopoietic stem cell transplant. Methods We collected clinical and microbiological data of patients with hematologic malignancies and breakthrough candidemia from a single center. Seven-day and 30-day follow-up outcomes were recorded; the incidence and mortality of breakthrough candidemia between patients who did or did not undergo an allogeneic transplant were compared. Kaplan-Meier survival estimates were used to generate survival curves, and predictors were identified using Cox regression analyses. Results Of 71 enrolled patients, 17 received allogeneic transplants. Incidences of breakthrough candidemia were 17 of 2924 (0.58%) and 54 of 12 015 (0.45%) in the transplant and nontransplant groups, respectively (P = .35). The most common isolate was Candida tropicalis, and antifungal agent combinations were the most common first-line treatment. Cumulative mortality rates of patients were 21.1% and 31.0% at days 7 and 30, respectively, and they significantly differed between both groups. Septic shock, central venous catheter removal, and granulocyte recovery were significantly associated with 7-day mortality; the latter 2 remained independent predictors of 30-day mortality. Conclusions Breakthrough candidemia-related mortality was higher in the allogeneic transplant group, although the incidence was not significantly different between the groups. Prompt and adequate antifungal treatment with catheter removal may reduce mortality.

Download Full-text

Red Blood Cell And Platelet Transfusions As Risk Factors For The Development Of Idiopathic Pneumonia Syndrome After Hematopoietic Stem Cell Transplant

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a1641 ◽

2011 ◽

Author(s):

Timothy R. Watkins ◽

Katherine A. Guthrie ◽

David K. Madtes

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Blood Cell ◽

Hematopoietic Stem Cell ◽

Red Blood Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Idiopathic Pneumonia Syndrome

Download Full-text

RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

Case Reports in Medicine ◽

10.1155/2011/830769 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Dânia Sofia Marques ◽

Carlos Pinho Vaz ◽

Rosa Branca ◽

Fernando Campilho ◽

Catarina Lamelas ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Unrelated Donor ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Increased Risk

Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due toRhizomucor sp.and rhinoencephalitis due toScedosporium apiospermum6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis), its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies).

Download Full-text