Assessment of Late Mortality Risk After Allogeneic Blood or Marrow Transplantation Performed in Childhood

Holmqvist, Anna Sällfors; Chen, Yanjun; Wu, Jessica; Battles, Kevin; Bhatia, Ravi; Francisco, Liton; Hageman, Lindsey; Kung, Michelle; Ness, Emily; Parman, Mariel; Salzman, Donna; Wadhwa, Aman; Winther, Jeanette Falck; Rosenthal, Joseph; Forman, Stephen J.; Weisdorf, Daniel J.; Armenian, Saro H.; Arora, Mukta; Bhatia, Smita

doi:10.1001/jamaoncol.2018.2453

Cited by 29 publications

(32 citation statements)

References 21 publications

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“…Overall, they noted that the cumulative incidence of late mortality decreased significantly over time from 1990 to 2010. 13 In 2007, Bhatia et al 14 reported 5-and 10-year survival outcomes in patients with SAA of 96% and 94%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases

Kahn

Brazauskas

Tecca³

et al. 2020

Blood Advances

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We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range, <1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was <1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.

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Section: Discussionmentioning

confidence: 99%

Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases

Kahn

Brazauskas

Tecca³

et al. 2020

Blood Advances

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“…Cardiovascular disease has been shown to be a leading cause of late morbidity and mortality after allo-HSCT [ 2 ] and survivors of allo-HSCT have a 4-fold higher risk of developing cardiovascular disease when compared with the general population [ 6 ]. A report from the Blood and Marrow Transplant Survivor Study-2 provided data on cause-specific late mortality after allo-HSCT [ 36 ]. In a large cohort ( n = 764), the most common causes of death among those surviving > 10 years were secondary malignancies (36%), infection (22%), and cardiac disease (14%).…”

Section: Discussionmentioning

confidence: 99%

Determinants of cardiorespiratory fitness in very long-term survivors of allogeneic hematopoietic stem cell transplantation: a national cohort study

Myrdal

Diep

Brinch

et al. 2020

Support Care Cancer

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Purpose Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for cardiopulmonary adverse events. Data on long-term effects on cardiorespiratory fitness are limited. To address the gap in knowledge, we aimed to determine peak oxygen uptake (V̇O2peak) and identify associations between cardiorespiratory fitness and clinical characteristics, self-reported physical activity, cardiac, and pulmonary function. Methods In a nationwide, single-center cross-sectional study, 90 survivors [aged median (range) 35 (17–54) years, 56% females] were examined, 17 (6–26) years after allo-HSCT. Myeloablative conditioning comprised busulfan/cyclophosphamide or cyclophosphamide only. Methods included pulmonary function tests, echocardiography, and cardiopulmonary exercise test. Results Chronic graft-versus-host disease (cGVHD) was found in 31% of the subjects, of whom 40% had bronchiolitis obliterans syndrome (BOS). Seventy-one percent of the survivors did not meet WHO recommendations for physical activity and 42% were overweight. Reduced gas diffusion (DLCO) and systolic ventricular dysfunction (LVEF) were found in 44% and 31%, respectively. For the group, mean (95% CI), V̇O2peak was 36.4 (34.7–38.0) mL/min/kg [89 (85–93)% of predicted]. V̇O2peak was low at 43%. Cardiopulmonary factors and deconditioning were equally common limitations for exercise. In a multiple linear regression model, low V̇O2peak was associated with low DLCO, low LVEF, BOS, overweight, and inactivity. Conclusion Half of the survivors had reduced cardiorespiratory fitness median 17 years after allo-HSCT. Cardiopulmonary factors and deconditioning were equally common limitations to exercise. We encourage long-term cardiopulmonary monitoring of allo-HSCT survivors and targeted advice on modifiable lifestyle factors.

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“…The probability of long-term survival after hematopoietic cell transplantation (HCT) has steadily improved in the last decade with advances in treatments (1,2). However, long term survival after HCT is still hampered by adverse events, such as graft-versus-host disease (GvHD), infections and relapse of the underlying disease (3)(4)(5)(6). Delayed immune reconstitution plays a central role in most of these events (7,8), suggesting that strategies that increase immune recovery are of great interest to increase survival chances post-HCT (9).…”

Section: Introductionmentioning

confidence: 99%

Immune Monitoring After Allogeneic Hematopoietic Cell Transplantation: Toward Practical Guidelines and Standardization

2020

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Hematopoietic cell transplantation (HCT) is often a last resort, but potentially curative treatment option for children suffering from hematological malignancies and a variety of non-malignant disorders, such as bone marrow failure, inborn metabolic disease or immune deficiencies. Although efficacy and safety of the HCT procedure has increased significantly over the last decades, the majority of the patients still suffer from severe acute toxicity, viral reactivation, acute or chronic graft-versus-host disease (GvHD) and/or, in case of malignant disease, relapses. Factors influencing HCT outcomes are numerous and versatile. For example, there is variation in the selected graft sources, type of infused cell subsets, cell doses, and the protocols used for conditioning, as well as immune suppression and treatment of adverse events. Moreover, recent pharmacokinetic studies show that medications used in the conditioning regimen (e.g., busulphan, fludarabine, anti-thymocyte globulin) should be dosed patient-specific to achieve optimal exposure in every individual patient. Due to this multitude of variables and site-specific policies/preferences, harmonization between HCT centers is still difficult to achieve. Literature shows that adequate immune recovery post-HCT limits both relapse and non-relapse mortality (death due to viral reactivations and GvHD). Monitoring immune parameters post-HCT may facilitate a timely prediction of outcome. The use of standardized assays to measure immune parameters would facilitate a fast comparison between different strategies tested in different centers or between different clinical trials. We here discuss immune cell markers that may contribute to clinical decision making and may be worth to standardize in multicenter collaborations for future trials.

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Assessment of Late Mortality Risk After Allogeneic Blood or Marrow Transplantation Performed in Childhood

Abstract: Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.

Cited by 29 publications

References 21 publications

Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases

Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases

Determinants of cardiorespiratory fitness in very long-term survivors of allogeneic hematopoietic stem cell transplantation: a national cohort study

Immune Monitoring After Allogeneic Hematopoietic Cell Transplantation: Toward Practical Guidelines and Standardization

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