Identifying risk factors associated with worse outcomes in adolescents and young adults undergoing hematopoietic stem cell transplantation.


Journal

Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624

Informations de publication

Date de publication:
12 2019
Historique:
received: 25 03 2019
revised: 07 07 2019
accepted: 11 07 2019
pubmed: 21 8 2019
medline: 17 3 2020
entrez: 21 8 2019
Statut: ppublish

Résumé

Adolescents and young adults (AYAs) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) have unique risk factors and poor outcomes when compared to children, but this population has not been well studied. A hematopoietic stem cell transplantation-comorbidity index (HCT-CI) has been developed in adults to help predict outcomes, yet this index does not seem suitable for a younger population. Therefore, we sought to examine the prevalence of various risk factors in AYAs undergoing allogeneic HSCT and determine which factors had the greatest impact on overall survival (OS) and treatment-related mortality (TRM). This was accomplished by retrospectively collecting data on 241 patients who received their first allogeneic HSCT at UCLA between 2005 and 2015. We investigated the effect of multiple predictors using the Cox proportional hazards model and Fine and Gray competing risk model for OS and TRM, respectively. Our results showed that AYAs undergoing allogeneic HSCT had poor outcomes, with 5-year OS and NRM of 48% and 30%, respectively. We demonstrated that compared to a baseline model, the addition of the HCT-CI did not improve its ability to predict OS, while substituting individual comorbidities, that is, an unweighted comorbidity score, resulted in significant improvement in model performance. The factors associated with inferior outcomes were used to develop an AYA-specific risk score. The comorbidities included in the HCT-CI as well as additional risk factors seen in younger populations need to be studied in prospective studies with the goal of validating and refining a risk score specific to AYA patients undergoing allogeneic HSCT.

Sections du résumé

BACKGROUND
Adolescents and young adults (AYAs) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) have unique risk factors and poor outcomes when compared to children, but this population has not been well studied. A hematopoietic stem cell transplantation-comorbidity index (HCT-CI) has been developed in adults to help predict outcomes, yet this index does not seem suitable for a younger population. Therefore, we sought to examine the prevalence of various risk factors in AYAs undergoing allogeneic HSCT and determine which factors had the greatest impact on overall survival (OS) and treatment-related mortality (TRM).
PROCEDURES
This was accomplished by retrospectively collecting data on 241 patients who received their first allogeneic HSCT at UCLA between 2005 and 2015. We investigated the effect of multiple predictors using the Cox proportional hazards model and Fine and Gray competing risk model for OS and TRM, respectively.
RESULTS
Our results showed that AYAs undergoing allogeneic HSCT had poor outcomes, with 5-year OS and NRM of 48% and 30%, respectively. We demonstrated that compared to a baseline model, the addition of the HCT-CI did not improve its ability to predict OS, while substituting individual comorbidities, that is, an unweighted comorbidity score, resulted in significant improvement in model performance. The factors associated with inferior outcomes were used to develop an AYA-specific risk score.
CONCLUSIONS
The comorbidities included in the HCT-CI as well as additional risk factors seen in younger populations need to be studied in prospective studies with the goal of validating and refining a risk score specific to AYA patients undergoing allogeneic HSCT.

Identifiants

pubmed: 31429528
doi: 10.1002/pbc.27940
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e27940

Informations de copyright

© 2019 Wiley Periodicals, Inc.

Références

Center for International Blood and Marrow Transplant, a contractor for the C.W. Bill Young Cell Transplantation Program operated through the U. S. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau. Demographics of HCT performed in the United States and reported to CIBMTR by donor type and cell source for each donor type. https://bloodcell.transplant.hrsa.gov/research/transplant_data/transplant_activity_report/index.html. Accessed September 20, 2018.
Burke MJ, Gossai N, Wagner JE, et al. Survival differences between adolescent/young adults and children with B-precursor acute lymphoblastic leukemia following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2013;19:138-142.
Tomizawa D, Tanaka S, Kondo T, et al. Allogeneic hematopoietic stem cell transplantation for adolescents and young adults with acute myeloid leukemia. Biol Blood Marrow Transplant. 2017;23:1515-1522.
Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912-2919.
Wood W, Deal A, Whitley J, et al. Usefulness of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) in predicting outcomes for adolescents and young adults with hematologic malignancies undergoing allogeneic stem cell transplant. Pediatr Blood Cancer. 2011;57:499-505.
Sorror ML, Logan BR, Zhu X, et al. Prospective validation of the predictive power of the hematopoietic cell transplantation comorbidity index: a CIBMTR® study. Biol Blood Marrow Transplant. 2015;21:1479-1487.
Raimondi R, Tosetto A, Oneto R, et al. Validation of the hematopoietic cell transplantation-specific comorbidity index: a prospective, multicenter GITMO study. Blood. 2012;120:1327-1333.
Smith AR, Majhail NS, MacMillan ML, et al. Hematopoietic cell transplantation comorbidity index predicts transplantation outcomes in pediatric patients. Blood. 2011;117:2728-2734.
Gramatges MM, Rabin KR. The adolescent and young adult with cancer: state of the art-acute leukemias. Curr Oncol Rep. 2013;15:317-324.
Mehta PA, Rotz SJ, Majhail NS. Unique challenges of hematopoietic cell transplantation in adolescents and young adults with hematologic malignancies. Biol Bone Marrow Transplant. 2018;24:e11-e19.
Kondryn HJ, Edmondson CL, Hill J, Eden TO. Treatment non-adherence in teenage and young adult patients with cancer. Lancet Oncol. 2011;12:100-108.
Burke ME, Albritton K, Marina N. Challenges in the recruitment of adolescents and young adults to cancer clinical trials. Cancer. 2007;110:2385-2393.
Nachman J, Sather HN, Buckley JD, et al. Young adults 16-21 years of age at diagnosis entered on Children's Cancer Group acute lymphoblastic leukemia and acute myeloblastic leukemia protocols. Results of treatment. Cancer. 1993;71:3377-3385.
Armand P, Gibson CJ, Cutler C, et al. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood. 2012;120:905-913.
Cox DR. Regression models and life-tables. J Royal Stat Soc. 1972;34:187-220.
Harrell FE, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247:2543-2546.
Harrell FE. Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis. New York: Springer-Verlag; 2013.
Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008;111:1827-1833.
Savani BN, Labopin M, Kröger N, et al. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT. Haematologica. 2016;101:773-780.
Paviglianiti A, Ruggeri A, Volt F, et al. Evaluation of a disease risk index for adult patients undergoing umbilical cord blood transplantation for haematological malignancies. Br J Haematol. 2017;179:790-801.
Beauverd Y, Roosnek E, Tirefort Y, et al. Validation of the disease risk index for outcome of patients undergoing allogeneic hematpoietic stem cell transplantation after T cell depletion. Biol Blood Marrow Transplant. 2014;20:1322-1328.
Muffly L. Patient selection for allogeneic hematopoietic cell transplantation (HCT): the evolution of HCT risk assessment. Curr Hematol Malig Rep. 2015;10:28-34.
Ljungman P, Perez-Bercoff L, Jonsson J, et al. Risk factors for the development of cytomegalovirus disease after allogeneic stem cell transplantation. Haematologica. 2006;91:78-83.
Loiseau P, Busson M, Balere M-L, et al. HLA association with hematopoietic stem cell transplantation outcome: the number of mismatches at HLA-A, -B, -C, -DRB1, or -DQB1 is strongly associated with overall survival. Biol Blood Marrow Transplant. 2007;13:965-974.
Wagner JE, Barker JN, DeFor TE, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood. 2002;100(5):1611-1618.
Eapen M, Rocha V, Sanz G, et al. Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukemia: a retrospective analysis. Lancet Oncol. 2010;11(7):653-660.
Fein JA, Shimoni A, Labopin M, et al. The impact of individual comorbidities on non-relapse mortality following allogeneic hematopoietic stem cell transplantation. Leukemia. 2018;32:1787-1794.
Khalil MMI, Lipton JH, Atenafu EG, et al. Impact of comorbidities constituting the hematopoietic cell transplant (HCT)-comorbidity index on the outcome of patients undergoing allogeneic HCT for acute myeloid leukemia. Eur J Haematol. 2018;100:198-205.
Figueroa Turienzo CM, Cernadas C, Roizen M, Pizzi S, Staciuk R. Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in a retrospective cohort of children and adolescents who received an allogeneic transplantation in Argentina. Arch Argent Pediatr. 2016;114:337-342.
Thakar MS, Broglie L, Logan B, et al. The hematopoietic cell transplant comorbidity index predicts survival after allogeneic transplant for nonmalignant diseases. Blood. 2019;133:754-762.
Campbell AP, Guthrie KA, Englund JA, et al. Clinical outcomes associated with respiratory virus detection before allogeneic hematopoietic stem cell transplant. Clin Infect Dis. 2015;61:192-202.
Fukuda T, Boeckh M, Guthrie KA, et al. Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10-year experience at a single transplant center. Biol Blood Marrow Transplant. 2004;10:494-503.
Huang T-T, Hudson MM, Stokes DC, Krasin MJ, Spunt SL, Ness KK. Pulmonary outcomes in survivors of childhood cancer. Chest. 2011;140:881-901.
Chi AK, Soubani AO, White AC, Miller KB. An update on pulmonary complications of hematopoietic stem cell transplantation. Chest. 2013;144:1913-1922.
Ramirez-Sarmiento A, Orozco-Levi M, Walter EC, Au MA, Chien JW. Influence of pretransplantation restrictive lung disease on allogeneic hematopoietic cell transplantation outcomes. Biol Blood Marrow Transplant. 2010;16:199-206.
Fadilah SAW, Aqilah MP. Promising role of reduced-toxicity hematopoietic stem cell transplantation (PART-I). Stem Cell Rev. 2012;8:1254-1264.
Weisdorf DJ. Reduced-intensity versus myeloablative allogeneic transplantation. Hematol Oncol Stem Cell Ther. 2017;10:321-326.
Kwak M, Zebrack BJ, Meeske KA, et al. Trajectories of psychological distress in adolescent and young adult patients with cancer: a 1-year longitudinal study. J Clin Oncol. 2013;31:2160-2166.
El-Jawahri A, Chen Y-B, Brazauskas R, et al. Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation. Cancer. 2017;123:1828-1838.
Prieto JM, Atala J, Blanch J, et al. Role of depression as a predictor of mortality among cancer patients after stem-cell transplantation. J Clin Oncol. 2005;23:6063-6071.
Knight JM, Lyness JM, Sahler OJZ, Liesveld JL, Moynihan JA. Psychosocial factors and hematopoietic stem cell transplantation: potential biobehavioral pathways. Psychoneuroendocrinology. 2013;38:2383-2393.
DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101.
Pai ALH, Rausch J, Drake S, et al. Poor adherence is associated with more infections following pediatric hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2018;24:381-385.
Sawyer SM, Drew S, Yeo MS, Britto MT. Adolescents with a chronic condition: challenges living, challenges treating. Lancet. 2007;369:1481-1489.
Olbrisch ME, Levenson JL, Hamer R. The PACT: a rating scale for the study of clinical decision-making in psychosocial screening of organ transplant candidates. Clin Transplant. 1989;3:164-169.
Foster LW, McLellan L, Rybicki L, Dabney J, Visnosky M, Bolwell B. Utility of the PACT scale in allogeneic BMT. Bone Marrow Transplant. 2009;44:375-380.
Hong S, Rybicki L, Abounader L, et al. Pretransplant psychosocial assessment and outcomes of allogeneic hematopoietic cell transplantation in adults. Blood. 2016;128:3552.
Nickel RS, Kamani NR. Ethical challenges in hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2018;24:219-227.
Pavliglianiti A, Dalle JH, Ayas M, et al. Low body mass index is associated with increased risk of acute GVHD after umbilical cord blood transplantation in children and young adults with acute leukemia: a study on behalf of Eurocord and the EBMT pediatric disease working party. Biol Blood Marrow Transplant. 2018;24:799-805.
Hansson ME, Norlin AC, Omazic B, et al. Vitamin D levels affect outcome in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20:1537-1543.
Wallace G, Jodele S, Howell J, et al. Vitamin D deficiency and survival after hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2015;21:1627-1631.
Verdi Schumacher M, Moreira Faulhaber GA. Nutritional status and hyperglycemia in the peritransplant period: a review of associations with parenteral nutrition and clinical outcomes. Rev Bras Hematol Hemoter. 2017;39:155-162.
Chee L, Tacey M, Lim B, et al. Pre-transplant ferritin, albumin, and haemoglobin are predictive of survival outcome independent of disease risk index following allogeneic stem cell transplantation. Bone Marrow Transplant. 2017;52:870-877.
Vaughn JE, Storer BE, Armand P, et al. Design and validation of an augmented hematopoietic cell transplantation-comorbidity index comprising pretransplant ferritin, albumin, and platelet count for prediction of outcomes after allogeneic transplantation. Biol Blood Marrow Transplant. 2015;21:1418-1424.

Auteurs

Brian D Friend (BD)

Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, California.
Department of Pediatrics, Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.

Kevin Tang (K)

Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, California.

Daniela Markovic (D)

Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, California.

David Elashoff (D)

Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, California.

Theodore B Moore (TB)

Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, California.

Gary J Schiller (GJ)

Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.

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