Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients.

Goldberg, SL; Klumpp, Thomas R.; Magdalinski, A. J.; Mangan, Kenneth F.

doi:10.1200/jco.1998.16.12.3796

Cited by 60 publications

(38 citation statements)

References 8 publications

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“…Indeed, the treatment-related mortality has decreased from 7.3 % for the period between 1995 and 2000 to 1.3 % during the period from 2000 to 2007 [20]. The reduction in mortality can be attributed to the selection of patients with better overall performance status for HSCT, a variable known to correlate with regimenrelated mortality [43], combined with improvements in supportive care and the increasing experience of caring for MS patients at transplant centers.…”

Section: Lesson 2: Increasing Experience Using Hsct For Patients Withmentioning

confidence: 99%

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Atkins

Freedman

2013

Neurotherapeutics

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Reports from more than 600 hematopoietic stem cell transplants (HSCT) have appeared in the medical literature for the last 1 and one-half decades. The patient's own stem cells are harvested and stored temporarily while high doses of chemotherapy and biologics are used to destroy the auto-destructive immune system. The immune system is regenerated from the infused autologous hematopoietic stem cells. Increasing clinical experience has refined patient selection criteria and management in the peri-transplant period leading to a reduction in treatment-related complications. HSCT, when used to treat patients with aggressive highly active multiple sclerosis, can reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients, in the absence of chronic treatment with disease-modifying agents. The top 10 lessons learned from the growing experience using HSCT for the treatment of multiple sclerosis are discussed.Keywords Hematopoietic stem cell transplantation . Multiple sclerosis . Autoimmunity . Immune ablation There are published reports of more than 600 bone marrowbased transplants performed primarily for the treatment of multiple sclerosis (MS). This review will focus on why and how the hematopoietic stem cell transplantation (HSCT) procedure is used and discuss some of the lessons that can be gleaned from the experience of using HSCT to treat MS.MS is an organ-specific autoimmune disease that results in exclusive central nervous system (CNS) demyelination and axonal damage. Early on, multifocal localized pockets of inflammation lead to transient neurologic dysfunction manifesting as a series of relapses followed by remissions, usually with complete recovery owing to adequate CNS repair. However, as the damage accumulates, repair becomes inadequate and leads to incomplete resolution of disability, culminating in a neurodegenerative process amid a sea of smoldering and changing inflammation. This is probably the underlying state for the clinical stage of secondary progressive MS (SP-MS), a phase characterized by relentless and progressive accumulation of neurological disability with dwindling evidence of discrete relapses [1].Targeting inflammation with interferon-β, glatiramer acetate, natalizumab, fingolimod, and other immune-modulating agents reduces the frequency of relapses, but the impact on delaying the onset, preventing or slowing the tempo of SP-MS remains uncertain [2][3][4]. Several other drugs are in late stage clinical trials and may provide new alternatives for some patients with relapsing-remitting MS (RR-MS). However, despite these therapeutic advances, a subset of patients seem refractory and rapidly develop severe neurological impairment, whereas other patients may have a slower progression of illness that ultimately results in marked functional disabilities. Only a single agent, mitoxantrone, has been shown to temporarily halt or slow the tempo of SP-MS [5,6], but even then, this occurs only in SP-MS patients who have highly act...

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Section: Lesson 2: Increasing Experience Using Hsct For Patients Withmentioning

confidence: 99%

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Atkins

Freedman

2013

Neurotherapeutics

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“…104 On the other hand, three studies reported a significant association between pre-transplant LVEF and cardiotoxicity 18,54,77 and two more described a trend in the same direction. 76,101 However, measurement of LVEF before HD chemotherapy is of limited practical value: increased rates of minor cardiac events, rather than increased mortality due to severe cardiac toxicity, were recorded among patients with diminished (ie 50-54%) baseline LVEF, and 2/3 major cardiac events occurred in patients with normal LVEF. 100 Overall, resting LVEF measurement in every HD chemotherapy candidate is not recommended; 76,100 published evidence 7,25,76,79,100,106 suggests that for patients undergoing front-line HD chemotherapy cardiologic evaluation including a detailed history, physical examination, chest X-ray and resting ECG is likely to be a sufficient screening tool to recognize candidates at high risk for cardiac complications.…”

Section: Predictive Value Of Pre-hd Chemotherapy Cardiologic Evaluatimentioning

confidence: 99%

Cardiac toxicity of high-dose chemotherapy

Morandi

Ruffini

Benvenuto

et al. 2004

Bone Marrow Transplant

151

104

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Summary:Cardiac toxicity is an uncommon but potentially serious complication of high-dose (HD) chemotherapy and little is known about incidence, severity and underlying mechanisms. We have systematically reviewed the literature of the last 30 years to summarize and appraise the published evidence on cardiac toxicity associated with HD chemotherapy. HD cyclophosphamide-containing regimens have been most commonly associated with cardiac toxicity, with a progressively decreasing incidence over time. Dosage, application regimens and coadministration of other chemotherapeutic agents emerged as risk factors. While cardiac toxicity has been rarely associated with other cytotoxic drugs, an unexpected incidence of severe cardiotoxicity resulted from reduced-intensity conditioning regimens containing melphalan and fludarabine. Predictive value of cardiologic examination of patients is limited, and patients with a slight depression of cardiac performance could tolerate HD chemotherapy. Clinical examination, resting electrocardiography and dosage adjustment in overweight patients remain the mainstay of prevention, with bidimensional echocardiography (2D echo) for patients with a history of anthracycline exposure. Strategies to decrease the long-term negative impact of anthracycline administration on cardiac performance are being investigated. New 2D echo-based techniques and circulating markers of cardiac function hold promise for allowing identification of patients at high risk for and early diagnosis of cardiac toxicity.

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“…29 Abnormal liver (primarily elevated serum transaminases) and renal (primarily elevated serum creatinine) function tests have been studied for prediction of early mortality. 27 Post-HCT sinusoidal obstruction syndrome and liver injury have been frequently seen among patients with pre-HCT elevated transaminase values or chronic hepatitis. 30 -32 Elevated pre-HCT serum creatinine was found to be a risk factor for post-HCT acute renal failure and mortality.…”

Section: Historical Studies On Impacts Of Single-organ Comorbidity Onmentioning

confidence: 99%

“…Low pre-transplant diffusion capacity of the lung for carbon monoxide (D L CO) was found to be associated with post-HCT death, but not due to respiratory failure, 24 while low forced expiratory volume in 1-second (FEV 1 ) was a risk factor for cytomegalovirus-associated interstitial pneumonitis. 25 Recent studies have identified the two abnormalities to be the most uncorrelated pulmonary-function test variables, 26 to predict mortality 26,27 and decline in lung functions after HCT, 28 and to differentiate between the insults of regimens with different intensities. 29 Abnormal liver (primarily elevated serum transaminases) and renal (primarily elevated serum creatinine) function tests have been studied for prediction of early mortality.…”

Section: Historical Studies On Impacts Of Single-organ Comorbidity Onmentioning

confidence: 99%

Comorbidities and Hematopoietic Cell Transplantation Outcomes

Sorror

2010

Hematology

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Conventional allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment option for various hematological diseases due, in part to high-dose conditioning and, in part, to graft-versus-tumor effects. Reduced-intensity or non-myeloablative conditioning regimens have relied mostly on graft-versus-tumor effects for disease control, and their advent has allowed relatively older and medically infirm patients to be offered allo-HCT. However, both HCT modalities have been associated with organ toxicities and graft-versus-host disease, resulting in substantial non-relapse mortality. It has become increasingly important to optimize pre-transplant risk assessment in order to improve HCT decision making and clinical trial assignments. Single-organ comorbidity involving liver, lung, heart, or kidney before HCT has been traditionally found to cause organ toxicity after HCT. Recent efforts have resulted in the advent of a weighted scoring system that could sensitively capture multiple-organ comorbidities prior to HCT. The HCT-comorbidity index (HCT-CI) has provided better prediction of HCT-related morbidity and mortality than other non-HCT-specific indices. Subsequent studies, with the exception of a few studies with modest numbers of patients, have confirmed the prognostic importance of the HCT-CI. Further, the HCT-CI has been consolidated with various disease-specific and patient-specific risk factors to refine assignments of patients to the appropriate HCT setting. Ongoing studies are addressing prospective validation of the HCT-CI, furthering our understanding of biological aging, and enhancing the applicability of the HCT-CI comorbidity coding. Future knowledge of the impacts of multiple comorbidities on post-HCT toxicities might guide new prophylactic and therapeutic interventions to lessen the procedure's mortality.

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Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients.

Abstract: The pretransplant evaluation is a useful tool to identify patients at risk for early toxic mortality following high-dose therapy.

Cited by 60 publications

References 8 publications

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Cardiac toxicity of high-dose chemotherapy

Comorbidities and Hematopoietic Cell Transplantation Outcomes

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