Cardiac Systolic Function in Patients Receiving Hematopoetic Stem Cell Transplantation: Risk Factors for Posttransplantation Cardiac Toxicity

doi:10.1016/j.transproceed.2007.11.077

Transplantation Proceedings

Volume 40, Issue 5, June 2008, Pages 1586-1590

https://doi.org/10.1016/j.transproceed.2007.11.077 Get rights and content

Abstract

One hundred eleven patients who received 125 hematopoetic stem cell transplantations (HSCT) with myeloablative conditioning regimens were retrospectively evaluated for the development of cardiac toxicity (CT). The aims of this study were to assess the frequency of cardiac complications in patients receiving HSCT and to investigate the value of pretransplantation variables to predict posttransplantation CT. Severe grade III–IV CT was not observed in this cohort, in whom pretransplantation eligibility criteria excluded the patients with a left ventricular ejection fraction (LVEF) of 50% or less. Grade I–II CT was seen in 13.4% patients. Patients with a history of previous mediastinal radiotherapy, high doses of anthracycyclines, and a longer interval between diagnosis and treatment were found to have higher risk of developing CT. Pretransplantation ferritin levels and the type of HSCT did not seem to have an effect on posttransplantation cardiac complications. Our results indicated that CT was managable in patients with a LVEF of at least 50%.

Section snippets

Patients

We retrospectively analyzed the acute CT in 111 consecutive patients (43 females, 68 males) who had undergone 125 HSCTs, including 14 patients with double/tandem transplants between September 2003 and December 2006. Of the 125 HSCT, 52 were autologous and 73 allogeneic transplants. Twenty-six patients had acute myeloid leukemia (AML), 15 had acute lymphoblastic leukemia (ALL), 35 had multiple myeloma (MM), 10 had severe aplastic anemia (SAA), 8 had non-Hodgkin's Lymphoma (NHL), 13 had Hodgkin's

Results

Before HSCT, the LVEF evaluated by echocardiography was ≥50% in all patients (range, 50–77; mean %, 65.9 ± 5.1) and the mean LVEF evaluated with RVG was 55.6 ± 7.4 (range, 36.0–74.0; n = 92). Pretransplantation LVEF values measured with echocardiography significantly correlated with RVG (P = .02). CT was diagnosed in 17 (13.4%) patients. There was grade I CT in 11 patients (8.7%), and grade II in 6 patients (4.7%). Three patients had asymptomatic, repeating, temporary arrythmias; 6 patients had

Discussion

High-dose cytotoxic chemoradiotherapy is a major challenge for organ functions. Lung, kidneys, liver, and gastrointestinal mucosa are particularly vulnerable to the myeloablative conditioning protocols of HSCT. CT is relatively less frequent in HSCT patients compared with other major organ toxicities. Similarly, we have not seen grade III–IV CT in our cohort of 125 HSCT, whereas grade I–II toxicities were seen in 13.4% of patients. Considering the fact that most patients received high-dose

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Hematopoietic cell transplantation for Mucopolysaccharidosis I in the presence of decreased cardiac function
2023, Molecular Genetics and Metabolism
Severe mucopolysaccharidosis type I, (MPS IH) is a rare inherited lysosomal disorder resulting in progressive storage of proteoglycans (GAGs) in central nervous system and somatic tissues and, if left untreated, causing death within the first decade of life. Hematopoietic cell transplantation (HCT) arrests many of the features of MPS IH but carries a 10–15% risk of mortality. Decreased cardiac function can occur in MPS IH and increase the risk of HCT.
Retrospective chart review was performed to determine the long-term outcome of individuals evaluated for HCT with MPS IH who had decreased cardiac function as measured by cardiac echocardiogram (echo) and ejection fraction (EF) of <50% at the time of initial evaluation.
Six patients ranging in age from 1 week to 21 months (median: 4 months) had EFs ranging from 25 to 47% (median: 32%) at diagnosis and were initiated on enzyme replacement therapy (ERT) with improvement in EF in three patients by 5 months. The remaining three patients continued to have EFs <50% and continuous milrinone infusion was added in the pre-HCT period. On average, milrinone infusion was able to be discontinued post-HCT, prior to hospital discharge, within a mean of 37 days. Five patients survived HCT and are alive today with normal EFs. One patient receiving milrinone died of sepsis during HCT with a normal EF.
Decreased cardiac systolic function in infants with MPS IH that fails to normalize with ERT alone may benefit from the addition of continuous milrinone infusion during HCT.
A Prognostic Model Based on Clinical Biomarkers for Heart Failure in Adult Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
2023, Transplantation and Cellular Therapy
Heart failure (HF) is an uncommon but serious cardiovascular complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, knowledge about early mortality prognostic factors in patients with HF after allo-HSCT is limited, and an easy-to-use prognostic model is not available. This study aimed to develop and validate a clinical-biomarker prognostic model capable of predicting HF mortality following allo-HSCT that uses a combination of variables readily available in clinical practice. To investigate this issue, we conducted a retrospective analysis at our center with 154 HF patients who underwent allo-HSCT between 2008 and 2021. The patients were separated according to the time of transplantation, with 100 patients composing the derivation cohort and the other 54 patients composing the external validation cohort. We first calculated the univariable association for each variable with 2-month mortality in the derivation cohort. We then included the variables with a P value <.1 in univariate analysis as candidate predictors in the multivariate analysis using a backward stepwise logistic regression model. Variables remaining in the final model were identified as independent prognostic factors. To predict the prognosis of HF, a scoring system was established, and scores were assigned to the prognostic factors based on the regression coefficient. Finally, 4 strongly significant independent prognostic factors for 2-month mortality from HF were identified using multivariable logistic regression methods with stepwise variable selection: pulmonary infection (P = .005), grade III to IV acute graft-versus-host disease (severe aGVHD; P = .033), lactate dehydrogenase (LDH) >426 U/L (P = .049), and brain natriuretic peptide (BNP) >1799 pg/mL (P = .026). A risk grading model termed the BLIPS score (for BNP, LDH, cardiac troponin I, pulmonary infection, and severe aGVHD) was constructed according to the regression coefficients. The validated internal C-statistic was .870 (95% confidence interval [CI], .798 to .942), and the external C-statistic was .882 (95% CI, .791-.973). According to the calibration plots, the model-predicted probability correlated well with the actual observed frequencies. The clinical use of the prognostic model, according to decision curve analysis, could benefit HF patients. The BLIPS model in our study can serve to identify HF patients at higher risk for mortality early, which might aid designing timely targeted therapies and eventually improving patients’ survival and prognosis.
Cardiotoxicity in Hematopoietic Stem Cell Transplant: Keeping the Beat
2020, Clinical Lymphoma, Myeloma and Leukemia
Citation Excerpt :
Almost all patients with diagnoses of leukemia or lymphoma in our study received anthracycline therapy; no independent correlation was found with exposure and CE. Current literature is discrepant in finding this variable predictive of a CE; our review found 4 studies to correlate10,12,24,46 and 2 that did not.8,9 Anthracycline is a mainstay of therapy and will, for the foreseeable future, contribute to Type I (irreversible) CT, whereas improved therapeutic radiation techniques contribute much less CT than previously.47
The number of hematopoietic stem cell transplants (HSCTs) performed in the United States and worldwide is increasing. Cardiac events have been well described in HSCT, and the incidence and type of cardiac events have not changed over recent decades.
This study adds to the body of evidence in describing the incidence and type of cardiac events experienced by an allogeneic and autologous HSCT population at a single institution from 2012 to 2017.
Sixty-five (9.8%) patients experienced cardiac events, including atrial arrhythmia (N = 39), acute heart failure (N = 9), acute coronary syndrome (N = 7), and new onset hypertension (N = 9), with a few instances of bradycardia, ventricular arrhythmia, pericardial effusion, and pericarditis. Our multivariable regression analysis identified age (older), creatinine (higher), and history of coronary artery disease to significantly correlate with risk of cardiac event (P = .005, P = .039, and P = .038, respectively). A subgroup analysis of those patients experiencing a cardiac event found pre-transplant atrial dilation by trans-thoracic echocardiogram to correlate with increased risk of atrial arrhythmia (33.8% vs. 9.7%; P = .03). Patients developing a CE had an increased risk of death within 1 year (11% vs. 32%; P < .001).
We review our results in context of other important HSCT cardiac studies to illuminate the most relevant factors of medical history, laboratory data, and cardiac measurements that will identify patients at higher risk, allowing for intervention to improve HSCT outcomes.
Prevalence of iron overload vs iron deficiency in multiple myeloma: Resembling or different from MDS - And stem cell transplant (SCT) - Patients?
2013, Clinical Lymphoma, Myeloma and Leukemia
Citation Excerpt :
In line with previous studies in patients with hematologic malignancies undergoing SCT, we also observed that the iron status correlates with organ function,6-8,30 assessing proBNP for cardiac function, eGFR for renal impairment, and CRP for patients' infectious status, showing that patients with either ID or IO had indeed elevated proBNP and CRP, and diminished eGFR values. This is in line with previous observations that both ID and IO serve as risk factors for posttransplantation cardiac toxicity.23,31 In accordance with these results, Anker et al demonstrated symptom relief in patients with chronic heart failure and ID after treatment with intravenous ferric carboxymaltose.28
Most MM patients develop anemia with progression to symptomatic disease. Usually, this is normocytic/normochromic, with normal or low iron and elevated ferritin levels. Because ferritin levels alone do not correctly reflect iron stores, we performed a comprehensive analysis of iron parameters (iron, ferritin, transferrin, transferrin saturation [TRFS]) to more precisely assess patients' iron metabolism.
We analyzed: (1) the frequency of IO vs. ID in 136 consecutive MM patients; (2) the prognostic effect on progression-free (PFS) and overall survival (OS); and (3) specific risk groups according to patients' iron metabolism.
Most patients had normal iron metabolism or ID: median iron, ferritin, transferrin, and TRFS values were 75 μg/dL, 446 μg/L, 195 mg/dL, and 26%, respectively. Ferritin levels of < 400 μg/L, 400 to 1000 μg/L, and > 1000 μg/L were observed in 46%, 30%, and 24%, and TRFS levels < 20%, 20% to 45%, and > 45% in 32%, 46%, and 22% of patients, respectively. When patients with modified (ID or IO) vs. normal iron metabolism were compared, laboratory parameters (prohormone of brain natriuretic peptide, estimated glomerular filtration rate, c-reactive protein, reflecting cardiac, renal, or infectious impairment), and PFS and OS appeared impaired with modified metabolism, albeit age- and disease-specific differences were insignificant.
Normal iron metabolism and ID is more frequent in MM patients than IO. ID and IO correlate with organ impairment and impaired survival in MM. This knowledge should be incorporated into the design of future studies that will determine the benefit of iron supplementation with ID, and iron chelators with IO in MM.
Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Low Left Ventricular Ejection Fraction
2009, Biology of Blood and Marrow Transplantation
Citation Excerpt :
Both NRM and OS in the study group are acceptable given the high-risk patient population, where 33 (59%) patients had relapsed or refractory disease and 14 (25%) were in second remission or beyond [3,9,10]. Cardiac toxicity in the immediate post-alllo-HCT period is reported in 0.9% to 43% of patients [2,11-17]. These complications include cardiomyopathy, arrhythmias, ischemic events, CHF, pericarditis, tamponade, and death because of cardiac compromise.
A high risk of regimen-related toxicity with allogeneic hematopoietic stem cell transplantation (allo-HSCT) limits this potentially curative treatment for patients with a left ventricular ejection fraction (LVEF) of ≥50%. We evaluated the frequency of cardiac complications and 100-day nonrelapse mortality (NRM) in 56 patients with a LVEF of ≤45%, who received allo HCT at our institution. The results were retrospectively compared with a matched control group with LVEF of ≥50%, which received an allogeneic stem cell transplantation (allo-SCT). After a median follow-up of 29 months in the study group, grade ≥2 cardiac complications were seen in 7 of 56 (12.5%) patients and cumulative incidence of 100-day NRM was 12.5% with no deaths from cardiac causes. In contrast, after a median follow-up of 49 months in the control group, grade >2 cardiac complications were seen in 19 of 161 patients (11.8%; P = 1.00) and cumulative incidence of 100-day NRM was 14.9% (P = .82). The presence of at least 1 of the 7 pretransplant cardiac risk factors (past history of smoking, hypertension, hyperlipidemia, coronary artery disease, arrhythmia, prior myocardial infarction, and congestive heart failure) was associated with a higher cardiac complication rate in the study group (P = .03). In conclusion, selected patients with a LVEF of ≤45% can safely receive allo-HCT without a significant increase in cardiac toxicity or NRM.
Incidence and predictors of severe cardiotoxicity in patients with severe aplastic anaemia after haploidentical haematopoietic stem cell transplantation
2019, Bone Marrow Transplantation

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Stem cellsCardiac Systolic Function in Patients Receiving Hematopoetic Stem Cell Transplantation: Risk Factors for Posttransplantation Cardiac Toxicity

Abstract

Section snippets

Patients

Results

Discussion

Blood

Eur J Cancer

Blood

Best Pract Res Clin Haematol

Blood

Am J Surg

Cardiac toxicity of bone marrow transplantation: predictive value of cardiologic evaluation before transplant

J Clin Oncol

Predictors for severe cardiac complications after hematopoietic stem cell transplantation

Bone Marrow Transplant

Stem cells
Cardiac Systolic Function in Patients Receiving Hematopoetic Stem Cell Transplantation: Risk Factors for Posttransplantation Cardiac Toxicity