Weight Gain in the First 10 Days after Hematopoietic Stem Cell Transplantation (HSCT) Is a Risk Factor for Early Mortality

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2471-2471 ◽  
Author(s):  
Lucila Nassif Kerbauy ◽  
Erika MM Costa ◽  
Juliano Cordova Vargas ◽  
Claudia Mac Donald Bley Nascimento ◽  
Joyce E Hyppolito ◽  
...  

Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for patients with hematological and neoplastic diseases. Despite recent improvements, HSCT is still associated with a significant risk of mortality. Determining risk factors for death within the first 100 days after HSCT could help to identify patients who would benefit from interventions in order to decrease that risk. We have previously reported that increased fluid accumulation during conditioning chemotherapy and in the early period after HSCT was associated with decreased survival (Costa EMM et al, ASH 2013Abstract #4512). Herein, we expand that series of patients and we further analyze the impact of weight gain on early (100-days) mortality in patients who underwent HSCT at our institution. Objective: To determine the impact of weight gain during the first 10 days post-HSCT on 100 days mortality. Methods:We retrospectively reviewed the medical charts of 331 patients who underwent HSCT at our institution from January, 2007 until December, 2013. Information on patients' body weight (BW) was measured daily, starting at admission. The highest BW recorded until until the first 10 days post-SCT (D+10) was used to calculate the BW increase in relation to the baseline BW. Based on our previous study, we used a cutoff of 6% gain in BW to identify a group of patients with increased risk of complications. The primary endpoint was mortality within 100 days post HSCT. Overall survival (OS) was estimated from the time of HSCT until death, and surviving patients were censored at last follow-up. A logistic regression model and a Cox model were fit to determine variables that predicted death within 100 days and OS, respectively. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: Median age was 43 years old (range <1 year-76 years) and 60% were male. HSC sources included autologous (46%), matched related donors (16%), matched unrelated donors (12%), cord blood units (16%) and mismatched related/unrelated donors (10%). Diagnosis included acute leukemia or chronic myeloid disorders (34%), lymphoma/multiple myeloma (42%) and non-malignant hematological disorders (24%). Twenty-one percent of patients had a ≥6% gain in BW until the first 10 days post-HSCT. These patients had developed an increased inflammatory state after the start of the conditioning regimen: there was no difference in baseline levels of C-reactive protein (4.8 mg/L vs. 7.4, p=0.37), but by D+10 patients who gained more BW had higher CRP (116.7 mg/L vs. 178.6 mg/L; p=0.01). Patients with increased gain in BW until D+10 had a decreased OS (HR 2.33, p<0.0001, 95% CI 1.45-3.73). The mortality within 100 days was 47% in the increased BW vs. 17% in the control group (p<0.0001). Among 18 patients who died within 100 days and had a ≥6% BW gain by D+10, causes of death included pneumonia (N=4), septic shock (N=9), fungal endocarditis (N=1), ischemic stroke (N=1) and disease progression (N=3). In a logistic regression analysis, after adjusting for age, sex, diagnosis and type of SCT, a ≥6% BW gain by D10 was associated with an increased risk of being dead within 100 days (coefficient 1.75; p<0.0001; 95% CI 0.90-2.61). Similarly, in a multivariate Cox analysis after adjusting for age, sex, diagnosis and type of SCT, a ≥6% BW gain by D10 was an independent risk factor for survival (HR 2.72, p<0.0001, 95% CI 1.65-4.48). A landmark analysis at D+100 revealed that the negative impact of weight gain by D+10 on survival was restricted to the first 100 days, as after this time point there was no survival difference between the two groups (HR 1.35; p=0.41; 95% CI 0.65-2.83). Conclusion: A ≥6% BW gain by D+10 is a risk factor for early mortality in both autologous and allogeneic HSCT. The most common cause of death in these patients is infectious-related complications. An increase in BW is related to the development of an inflammatory state, probably induced by the conditioning regimen. BW gain is a simple variable that can be easily used to determine prognosis of patients post-allogeneic HSCT, and further studies are needed to determine its etiology. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3061-3061 ◽  
Author(s):  
Alexander Claviez ◽  
Carmen Canals ◽  
Marc Boogaerts ◽  
Jerry Stein ◽  
Stephen Mackinnon ◽  
...  

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for patients with recurring Hodgkin’s lymphoma (HL). Standardized inclusion criteria, the optimal time point and the type of conditioning regimen have, however, not been clarified yet. Moreover, high treatment related mortality (TRM) has hampered the widespread use of this procedure. Only few data are available on the impact of allogeneic HSCT in pediatric and adolescent patients. Patients and Methods: We analyzed patients registered in the EBMT Lymphoma Database (age < 21 years at transplantation) who received an allogeneic HSCT for relapsed or refractory HL between 1987 and 2005. Results: A total of 151 patients (56% male) were included. Median age at diagnosis and HSCT was 15 and 18 years, respectively. 57% of patients had received three or more lines of treatment prior to allogeneic HSCT including autologous HSCT in 77 patients with a median interval of 18 months between autologous and allogeneic HSCT. The majority of donors were matched related (63%), followed by matched unrelated (25%) and mismatched donors. A full myeloablative conditioning regimen was given to 40% of patients and 60% received a regimen of reduced intensity. Disease status at HSCT was sensitive (complete or partial remission) in 59% and refractory (no change or progression) in 41%. 23% of the patients developed grade 2–4 acute graft versus host disease (GvHD). Of 35 patients with evaluable chronic GvHD, limited and extensive GvHD were balanced. With a median follow-up of 25 months (maximum 154), 75 patients (50%) are alive and 59 of them disease-free. 56 patients (37%) relapsed after a median time of 5 months (<1 to 36 months) and only 16 were alive at last contact. The probability for progression-free survival (PFS) at 2 and 5 years were 39% and 29% respectively. The cumulative incidences (CI) for relapse at 1, 2 and 5 years were 29%, 37% and 44%, respectively, whereas the CI for TRM at 1, 2 and 5 years were 20%, 24% and 27%, respectively. In multivariate analysis, HLA disparity (p=.002), HSCT before 2001 (p=.01) and female sex (p=.02) were associated with a higher TRM, while poor performance status (p=.005) and refractory disease (p=.04) resulted in an inferior PFS. Reduced treatment intensity had no impact on relapse rate within one year after HSCT but was associated with a higher incidence of relapse (p=.02) beyond 12 months. The PFS and TRM of patients without adverse prognostic factors (HSCT >2001, matched donors and good performance status at HSCT) at 1, 2 and 5 years was 67%, 50% and 43%, and 11%, 17% and 17%, respectively. Conclusion: This study of young patients with HL receiving allogeneic HSCT indicates a comparable outcome to adult patients. Transplantation was beneficial especially for patients with a good performance status, HSCT in recent years and available matched donors. Allogeneic HSCT should be carefully selected at an early time point in children failing standardized primary and salvage treatment.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4986-4986
Author(s):  
Enrico Morello ◽  
Irene M. Cavattoni ◽  
Pietro Fabris ◽  
Silvia Coin ◽  
Barbara Amato ◽  
...  

Abstract Background and aims IFIs still pose major challenges in HSCT, and effective prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the impact of aerosolized d-AmB on respiratory tract IFIs in a homogeneous cohort of allogeneic HSCT patients, transplanted at our institution. Patients and methods Since 1999, 81 consecutive patients were transplanted from matched related (N=61) or unrelated donor (MUD). Analysis was performed on 74 evaluable patients, in order to monitor the prevalence of respiratory tract IFIs within 40 days after HSCT, according to current guidelines (possible, probable, proven IFIs). Conventional antifungal prophylaxis was based on the association of fluconazole (400 mg/d), plus aerosolized d-AmB (15 mg bid) in 54 out of 74 cases (73%). All the patients were screened before transplant and monitored thereafter with CT or x-rays (paranasal sinuses, thorax), surveillance swabs and galactomannan antigenemia. Chi square test was performed to evaluate correlations between variables. Results Aerosolised d-AmB was administered to 70 patients for a median time of 15 days (range 1–45). Prolonged administration was not associated with increased severe bacterial infections, nor severe adverse events were observed; only a patient developed moderate bronchial spasm. In 13 pts, aerosolized d-AmB was delivered for less than 7 days, due to worsened clinical conditions, or poor compliance. In this group, proven IFIs were diagnosed in 2 patients (1 mucormycosis and 1 fusariosis), possible aspergillosis in one and probable aspergillosis in another one. A shortened administration (<7 days) of aerosolized d-AmB was associated with an increased risk of IFIs (p=0,002). Overall, 95% of patients did not experience IFIs and nobody died due to IFIs. Nine patients had a pre-transplant nasal swab positive for Aspergillus spp., and 8 of them received Aerosolized d-AmB; subsequent surveillance swabs proved negative. On the other hand, the only patient with positive swab who was not able to receive aerosolized d-AmB due to bronchial spasm developed a possible aspergillosis. Discussion Despite the low number of patients, prolonged aerosolized d-AmB seems to play a role in preventing respiratory tract IFIs, but a randomised controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5748-5748
Author(s):  
Gaetano Maffongelli ◽  
Gaetano Maffongelli ◽  
Gaetano Maffongelli ◽  
Laura Cudillo ◽  
Fabio Di Piazza ◽  
...  

Abstract Introduction: Outcome in allogeneic HSCT varies widely depending on disease type, stage, stem cell source, HLA-matched status and conditioning regimen. IFI is a possible complication of HSCT and a prior IFI increases the patient's risk for transplant related mortality due to the possibility of reactivation of the fungal infection. This study aimed to evaluate the impact of a previous IFI history on transplant outcome Methods: We retrospectively collected the clinical data of patients considered eligible for allogeneic HSCT during 2014 at the Rome Transplant Network (RTN), a JACIE accredited metropolitan transplant program established in Rome since 2006. The observation of patients was continued until 31 December 2015. The diagnosis of IFI were defined as possible, probable and proven as established by European Organization for Research and treatment of Cancer. Results: Twenty-one (37%) out of 57 eligible patients had an IFI episode before transplant: 6 of the episodes were proven, 4 probable and 11 possible. Overall, 10 (47%) pneumonia, 4 (19%) gastroenteritis, 3 sinusitis, 2 candida sepsis, 1 meningitis and 1 cutaneous abscess were registered. Five out of 21 patients (23%) died before HSCT versus 2 of 36 patients (5%) without previous documented IFI, [OR 5.31 95% CI 0.93- 30.40 , p value 0.06 Fisher Test], . A larger percentage of patients with past IFI waited HSCT over 6 months from the date of eligibility in comparison with those without previous IFI [43% vs 30% ; OR 1.87 95% CI 0.54-6.40 , p value 0.5 Yates test]; Sixteen (57%) out of 28 dead patients in the pre-transplant period have had a previous IFI episode vs 5(17%) out of patients alive [OR 6.4, 95% CI 1.89-21.68, p value: 0.004 Yates Test]. In the post-transplant period, only 6% of patients with a past IFI, experienced an engraftment in a time of < 15 days, vs 30% of patients without past IFI [OR 4.86 CI 95% 0,5-43,2, p value 0,2 Yates test]. In the post-transplant period, a IFI was diagnosed in 13 (26%) patients; ten (76%) out of 13 patients had a past IFI versus 9 (24%) of the patients without IFI.. [OR 7.87, CI 95% 1,8-34,2, p value 0,005 Yates test].Among the dead HSCT patients, those who had a previous IFI had a lower median survival [160 days (range 22- 480)] compared to patients without a previous IFI who died [196.5 days period (range 20-820)]. Conclusions: A previous IFI episode in the pre transplant period slow the accessibility to the transplant, adversely affects the engraftment, and is significantly associated with increased post-transplant mortality Disclosures No relevant conflicts of interest to declare.


2005 ◽  
Vol 23 (25) ◽  
pp. 6163-6171 ◽  
Author(s):  
Arturo Molina ◽  
Jasmine Zain ◽  
Daniel A. Arber ◽  
Maria Angelopolou ◽  
Margaret O’Donnell ◽  
...  

Purpose Sezary syndrome (SS) and tumor-stage mycosis fungoides (MF) are generally incurable with currently available treatments. We conducted a retrospective study to evaluate the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) in this patient population. Patient and Methods From August 1996 through October 2002, eight patients with advanced MF/SS underwent allogeneic HSCT at our institution. All patients were heavily pretreated, having failed a median number of seven prior therapies (range, five to 12). Clonal T-cell populations in peripheral blood or bone marrow were detectable by polymerase chain reaction analyses of T-cell receptor γ-chain gene rearrangements in six patients and cytogenetics in three patients. The conditioning regimen included total-body irradiation and cyclophosphamide (n = 3), busulfan and cyclophosphamide (n = 1), and the reduced-intensity regimen of fludarabine and melphalan (n = 4). Allogeneic hematopoietic stem cells were obtained from HLA-matched siblings (n = 4) and unrelated donors (n = 4). Results All patients achieved complete clinical remission and resolution of molecular and cytogenetic markers of disease within 30 to 60 days after HSCT. Two patients died from transplantation-related complications; graft-versus-host disease (GVHD; n = 1) and respiratory syncytial virus pneumonia (n = 1). With a median follow-up of 56 months, six patients remain alive and without evidence of lymphoma. Conclusion Our results suggest that allogeneic HSCT from both HLA–matched sibling and unrelated donors can induce durable clinical, molecular, and cytogenetic remissions in patients with advanced cutaneous T-cell lymphoma that is refractory to standard therapies.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xin He ◽  
YongBin Ye ◽  
XiaoJun Xu ◽  
Jing Wang ◽  
YuXian Huang ◽  
...  

Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a major cause of nonrelapse mortality after allo-HSCT. A conditioning regimen plays a pivotal role in the development of aGVHD. To provide a platform for studying aGVHD and evaluating the impact of different conditioning regimens, we established a murine aGVHD model that simulates the clinical situation and can be conditioned with Busulfan-Cyclophosphamide (Bu-Cy) and Fludarabine-Busulfan (Flu-Bu). In our study, BALB/c mice were conditioned with Bu-Cy or Flu-Bu and transplanted with 2×107 bone marrow cells and 2×107 splenocytes from either allogeneic (C57BL/6) or syngeneic (BALB/c) donors. The allogeneic recipients conditioned with Bu-Cy had shorter survivals (P<0.05), more severe clinical manifestations, and higher hepatic and intestinal pathology scores, associated with increased INF-γ expression and diminished IL-4 expression in serum, compared to allogeneic recipients conditioned with Flu-Bu. Moreover, higher donor-derived T-cell infiltration and severely impaired B-cell development were seen in the bone marrow of mice, exhibiting aGVHD and conditioned with Flu-Bu. Our study showed that the conditioning regimen with Bu-Cy resulted in more severe aGVHD while the Flu-Bu regimen was associated with more extensive and long standing bone marrow damage.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Andrzej Lange ◽  
Janusz Lange ◽  
Emilia Jaskuła

The COVID-19 pathomechanism depends on (i) the pathogenicity of the virus, (ii) ability of the immune system to respond to the cytopathic effect of the virus infection, (iii) co-morbidities. Inflammatory cytokine production constitutes a hallmark of COVID-19 that is facilitated by inability of adaptive immunity to control virus invasion. The effect of cytokine release syndrome is deleterious, but the severity of it depends on other confounding factors: age and comorbidities. In this study, we analyze the literature data on the post-transplant course of allogeneic hematopoietic stem cell transplanted (alloHSCT) patients, which is affected by generated inflammatory cytokines. The sequence of events boosting cytokine production was analyzed in relation to clinical and laboratory data highlighting the impact of cytokine generation on the post-transplant course. The collected data were compared to those from studies on COVID-19 patients. The similarities are: (i) the damage/pathogen-associated molecular pattern (DAMP/PAMP) stage is similar except for the initiation hit being sterile in alloHSCT (toxic damage of conditioning regimen) and viral in COVID-19; (ii) genetic host-derived factors play a role; (iii) adaptive immunity fails, DAMP signal(s) increases, over-production of cytokines occurs; (iv) monocytes lacking HLADR expression emerge, being suppressor cells hampering adaptive immunity; (v) immune system homeostasis is broken, the patient’s status deteriorates to bed dependency, leading to hypo-oxygenation and malnutrition, which in turn stimulates the intracellular alert pathways with vigorous transcription of cytokine genes. All starts with the interaction between DAMPs with appropriate receptors, which leads to the production of pro-inflammatory cytokines, the inflammatory process spreads, tissue is damaged, DAMPs are released and a vicious cycle occurs. Attempts to modify intracellular signaling pathways in patients with post-alloHSCT graft vs host disease have already been undertaken. The similarities documented in this study show that this approach may also be used in COVID-19 patients for tuning signal transduction processes to interrupt the cycle that powers the cytokine overproduction.


2014 ◽  
Vol 10 (01) ◽  
pp. 35 ◽  
Author(s):  
Abd A Tahrani ◽  
Asad Ali ◽  
◽  

With the growing prevalence of obesity, the burden of type 2 diabetes is increasing. Obstructive sleep apnea (OSA) is a very common medical condition that is associated with increased risk for cardiovascular disease and mortality. Obesity is a common risk factor for OSA and type 2 diabetes and hence it is not surprising that OSA and type 2 diabetes are interlinked. OSA has been shown to be an independent risk factor for the development of incident pre-diabetes/type 2 diabetes. OSA is also associated with worse glycemic control and vascular disease in patients with type 2 diabetes. However, evidence for the benefits of OSA treatment in patients with type 2 diabetes is still lacking. The aim of this article is to provide an overview of OSA, the relationships between OSA and dysglycemia and the impact of OSA in patients with type 2 diabetes, highlighting recent advances in the field.


2010 ◽  
Vol 28 (30) ◽  
pp. 4642-4648 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Mack ◽  
Michael Stoppel ◽  
Franz Király ◽  
...  

Purpose To assess the impact of allogeneic hematopoietic stem-cell transplantation (HSCT) from matched related donors (MRDs) and matched unrelated donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods Between 1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment strategy. High risk was defined by the presence of unfavorable cytogenetics and/or by no response to induction therapy. Results Two hundred sixty-seven (32%) of 844 patients were assigned to the high-risk group. Of these 267 patients, 51 patients (19%) achieved complete remission but had adverse cytogenetics, and 216 patients (81%) had no response to induction therapy. Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients, after a median time of 147 days after diagnosis. Graft sources were as follows: MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n = 1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from date of transplantation) for patients (n = 162) receiving HSCT. Multivariable analysis including allogeneic HSCT as a time-dependent covariable revealed that allogeneic HSCT significantly improved outcome; there was no difference in outcome between allogeneic HSCT from MRD and MUD. Conclusion Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.


2021 ◽  
Vol 15 (10) ◽  
pp. 2817-2819
Author(s):  
Ajwad Farogh ◽  
Asma Hassan ◽  
Saira Gull ◽  
Muhammad Irfan Khan ◽  
Gohar Bashir ◽  
...  

Background: Anemia is a common risk factor for cardiovascular disease. The impact of preoperative anaemia is unclear in cardiac surgery. Preoperative anaemia affects early findings in patients undergoing cardiac surgery. Aim and Objective: The main objective of current research was to investigate the impact of preoperative anaemia on early outcomes in heart surgery patients. Material and Methods: A prospective randomized clinical research was undertaken after obtaining written informed consent from patients for cardiac surgery at the PIC, Lahore between Apr 2020 and Feb 2021. A total of 120 individuals between the ages of 20 and 60 were chosen for the research. Preoperative anaemia was described as Hb levels of <13 g/dl for males and <12 g/dl in female patients undergoing cardiac surgery. Results: Total 120 patients were enrolled and stratified into two groups (60 patients each) with average age 5 ± 5.75 years. Early outcomes after surgery such as postoperative stroke (6.67 % versus 1.6 %), AF (37 % versus32 %), and duration of hospital stay > 7 days (50 % vs 41.67 %) were found to be different between anaemic and normal Hb groups. Conclusion: Preoperative anaemia can be increased risk of morbidity and mortality in patients after surgery. Low preoperative Hb found as advanced risk factor for death, renal impairment, stroke, AF and long hospital stay in our research. Keywords: Anemia, CABG, AF, MI, IABP, CPB


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