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• W2336931112 abstract "•T-cell replete peripheral blood stem cell (PBSC) allografts have significant graft-versus-leukemia benefits that are important drivers of improved leukemia-free survival and overall survival.•Patients who receive PBSC grafts have a higher incidence of acute and chronic graft-versus-host disease, both of which are associated with increased transplant-related mortality and long-term complications.•We support the use of PBSC over BM allografts in patients with acute leukemia who receive reduced-intensity conditioning. Over the past decade, transplantation of peripheral blood hematopoietic cells has increased and is now the predominant graft source for related or unrelated adult allogeneic hematopoietic stem cell transplantation. At the same time, increasing numbers of patients are receiving reduced-intensity conditioning (RIC) prior to hematopoietic stem cell infusion. In prior work using smaller patient numbers and limited data, RIC peripheral blood stem cell (PBSC) transplantation was shown to be noninferior to RIC bone marrow (BM) transplantation for acute leukemia. A recent, large registry analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation showed that peripheral blood grafts result in superior outcomes compared with BM after RIC regimens for acute leukemia. The T-cell-replete PBSC allografts are associated with significant graft-versus-leukemia (GVL) benefits that are important drivers of improved leukemia-free survival and overall survival. However, an increased risk of chronic graft-versus-host disease (cGVHD) after peripheral blood grafts is concerning and long-term follow-up comparing peripheral versus BM grafts after RIC regimens is needed. Further assessment of the long-standing risks should be undertaken in an effort to better understand whether the risk of cGVHD among peripheral blood graft recipients translates into continued GVL effects and long-term remissions and cures or if it results in late morbidity and mortality. Over the past decade, transplantation of peripheral blood hematopoietic cells has increased and is now the predominant graft source for related or unrelated adult allogeneic hematopoietic stem cell transplantation. At the same time, increasing numbers of patients are receiving reduced-intensity conditioning (RIC) prior to hematopoietic stem cell infusion. In prior work using smaller patient numbers and limited data, RIC peripheral blood stem cell (PBSC) transplantation was shown to be noninferior to RIC bone marrow (BM) transplantation for acute leukemia. A recent, large registry analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation showed that peripheral blood grafts result in superior outcomes compared with BM after RIC regimens for acute leukemia. The T-cell-replete PBSC allografts are associated with significant graft-versus-leukemia (GVL) benefits that are important drivers of improved leukemia-free survival and overall survival. However, an increased risk of chronic graft-versus-host disease (cGVHD) after peripheral blood grafts is concerning and long-term follow-up comparing peripheral versus BM grafts after RIC regimens is needed. Further assessment of the long-standing risks should be undertaken in an effort to better understand whether the risk of cGVHD among peripheral blood graft recipients translates into continued GVL effects and long-term remissions and cures or if it results in late morbidity and mortality. The acute leukemias are heterogeneous diseases that affect men and women of all ages and races, arise de novo or secondary to a genotoxic insult, and are associated with variable prognosis and survival [1Ezoe S. Secondary leukemia associated with the anti-cancer agent, etoposide, a topoisomerase II inhibitor.Int J Environ Res Public Health. 2012; 9: 2444-2453Crossref PubMed Scopus (115) Google Scholar, 2Radivoyevitch T. Sachs R.K. Gale R.P. et al.Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation.Leukemia. 2016; 30: 285-294PubMed Google Scholar, 3Bejar R. Steensma D.P. Recent developments in myelodysplastic syndromes.Blood. 2014; 124: 2793-2803Crossref PubMed Scopus (127) Google Scholar]. It is estimated that 20,830 people were diagnosed with acute myeloid leukemia (AML) in the United States in 2015 [4SEER stat fact sheets: acute myeloid leukemia (AML). Available at: http://seer.cancer.gov/statfacts/html/amyl.html. [Accessed Oct 26, 2015].Google Scholar]. With the incidence of AML increasing with age, there is a sizeable population at risk of developing this disease and in need of improved management strategies. Allogeneic hematopoietic stem cell transplantation (HCT) is an important tool in the management of patients with high-risk acute leukemias, but is associated with appreciable morbidity and mortality. With optimal treatment delivered under the most favorable circumstances, about one fourth of patients are alive at 5 years and ≤10% with poor-risk disease will survive beyond 10 years [4SEER stat fact sheets: acute myeloid leukemia (AML). Available at: http://seer.cancer.gov/statfacts/html/amyl.html. [Accessed Oct 26, 2015].Google Scholar, 5Grimwade D. Hills R.K. Moorman A.V. et al.Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials.Blood. 2010; 116: 354-365Crossref PubMed Scopus (1388) Google Scholar]. Even with favorable-risk, core-binding-factor AML, the 10-year mortality rate is 58% [6Appelbaum F.R. Kopecky K.J. Tallman M.S. et al.The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations.Br J Haematol. 2006; 135: 165-173Crossref PubMed Scopus (198) Google Scholar]. Allogeneic HCT in the setting of high-risk AML improves relapse-free survival (RFS) by 31% and overall survival (OS) by 27% [7Koreth J. Schlenk R. Kopecky K.J. et al.Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials.JAMA. 2009; 301: 2349-2361Crossref PubMed Scopus (639) Google Scholar]. Pediatric acute lymphoblastic leukemia (ALL) is associated with an excellent 5-year RFS and, in the salvage setting, rates of second complete remission (CR) exceed 90% [8Tzortzatou-Stathopoulou F. Papadopoulou A.L. Moschovi M. Botsonis A. Tsangaris G.T. Low relapse rate in children with acute lymphoblastic leukemia after risk-directed therapy.J Pediatr Hematol Oncol. 2001; 23: 591-597Crossref PubMed Scopus (18) Google Scholar, 9Ko R.H. Ji L. Barnette P. et al.Outcome of patients treated for relapsed or refractory acute lymphoblastic leukemia: a Therapeutic Advances in Childhood Leukemia Consortium study.J Clin Oncol. 2010; 28: 648-654Crossref PubMed Scopus (187) Google Scholar]. In contrast to pediatric ALL, adult ALL behaves more aggressively, and long-term outcomes are generally less favorable. A CR can be achieved in most adults with induction chemotherapy, but less than half of these patients will have durable remissions, and older patients are at the highest risk for relapse [10Larson R.A. Dodge R.K. Burns C.P. et al.A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811.Blood. 1995; 85: 2025-2037Crossref PubMed Google Scholar, 11Linker C. Damon L. Ries C. Navarro W. Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia.J Clin Oncol. 2002; 20: 2464-2471Crossref PubMed Scopus (159) Google Scholar, 12Kantarjian H. Thomas D. O'Brien S. et al.Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia.Cancer. 2004; 101: 2788-2801Crossref PubMed Scopus (437) Google Scholar, 13Rowe J.M. Buck G. Burnett A.K. et al.Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993.Blood. 2005; 106: 3760-3767Crossref PubMed Scopus (491) Google Scholar]. Salvage therapy seldom results in long-term disease control, and these patients face a median OS of <6 months. Less than 10% of patients with relapsed ALL will become long-term survivors [14Fielding A.K. Richards S.M. Chopra R. et al.Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study.Blood. 2007; 109: 944-950Crossref PubMed Scopus (574) Google Scholar, 15Oriol A. Vives S. Hernández-Rivas J.M. et al.Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group.Haematologica. 2010; 95: 589-596Crossref PubMed Scopus (197) Google Scholar]. Allogeneic HCT alters the disease course favorably in these patients compared with chemotherapy alone, and the best outcomes are reported when allografting is undertaken in the first CR [14Fielding A.K. Richards S.M. Chopra R. et al.Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study.Blood. 2007; 109: 944-950Crossref PubMed Scopus (574) Google Scholar, 16Mohty M. Labopin M. Tabrizzi R. et al.Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation.Haematologica. 2008; 93: 303-306Crossref PubMed Scopus (78) Google Scholar, 17Bachanova V. Verneris M.R. DeFor T. Brunstein C.G. Weisdorf D.J. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation.Blood. 2009; 113: 2902-2905Crossref PubMed Scopus (84) Google Scholar, 18Cho B.S. Lee S. Kim Y.J. et al.Reduced-intensity conditioning allogeneic stem cell transplantation is a potential therapeutic approach for adults with high-risk acute lymphoblastic leukemia in remission: results of a prospective phase 2 study.Leukemia. 2009; 23: 1763-1770Crossref PubMed Scopus (48) Google Scholar]. In the salvage setting, the CD19-bispecific T-cell engager blinatumomab and chimeric antigen receptor T (CART) cells have generated recent excitement; however, the long-term success of these agents remains uncertain [19Byrne M. Savani B.N. The devil is in the T-cells: Relapsing after haploidentical hematopoietic cell transplantation.Bone Marrow Transplant. 2016; ([In press])Google Scholar]. In 2005, the Acute Leukemia Working Party (ALWP) of the European Group for Blood and Marrow Transplantation (EBMT) compared reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens in AML patients ≥50 years of age. Both acute graft-versus-host disease (aGVHD) and transplant-related mortality (TRM) were significantly higher in patients who received MAC, whereas RIC was associated with a higher incidence of disease relapse. The OS between groups was not significantly different [20Aoudjhane M. Labopin M. Gorin N.C. et al.Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT).Leukemia. 2005; 19: 2304-2312Crossref PubMed Scopus (377) Google Scholar]. A study from the Center for International Blood and Marrow Transplantation Research (CIBMTR) looked at these approaches again in 2010. Patients who underwent RIC were older, had a lower Karnofsky Performance Status (KPS), and were less likely to go to transplantation with residual leukemia. Despite these differences, the DFS and OS between the groups were similar [21Luger S.M. Ringdén O. Zhang M.J. et al.Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDS.Bone Marrow Transplant. 2012; 47: 203-211Crossref PubMed Scopus (212) Google Scholar]. In a third analysis of myelodysplastic syndrome (MDS)/AML patients, RIC patients had a higher EBMT risk score (which correlates with higher TRM), were older, and received transplantation in later phases of their disease. Consistent with the prior studies, RIC led to a lower nonrelapse mortality (NRM), but these patients were more likely to relapse, resulting in an inferior 7-year OS [22Martino R. de Wreede L. Fiocco M. et al.Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with <10% BM blasts: a report from EBMT.Bone Marrow Transplant. 2013; 48: 761-770Crossref PubMed Scopus (78) Google Scholar, 23Gratwohl A. The EBMT risk score.Bone Marrow Transplant. 2012; 47: 749-756Crossref PubMed Scopus (203) Google Scholar]. It should be noted that RIC allografting can be safely undertaken in elderly patients. A CIBMTR analysis showed no differences in survival based on age, whereas a KPS of <80% had a negative impact on 2-year OS [24McClune B.L. Weisdorf D.J. Pedersen T.L. et al.Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome.J Clin Oncol. 2010; 28: 1878-1887Crossref PubMed Scopus (365) Google Scholar]. Recently, on behalf of the CIBMTR, Scott et al. [25Scott BL, Pasquini MC, Logan B, et al. Results of a phase III randomized, multi-center study of allogeneic stem cell transplantation after high versus reduced intensity conditioning in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0901. Paper presented at: American Society of Hematology 57th Annual Meeting and Exposition; December 5–8, 2015; Orlando, FL.Google Scholar] presented the results of their well-designed, two-arm trial in which patients were randomized to conventional RIC versus MAC. The study was stopped early because relapse rates were markedly higher in the RIC group. The reduction in NRM was not sufficient to compensate for this elevated risk, and the leukemia-free survival (LFS) was higher after MAC. The investigators concluded that MAC should remain the standard conditioning regimen for eligible patients [25Scott BL, Pasquini MC, Logan B, et al. Results of a phase III randomized, multi-center study of allogeneic stem cell transplantation after high versus reduced intensity conditioning in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0901. Paper presented at: American Society of Hematology 57th Annual Meeting and Exposition; December 5–8, 2015; Orlando, FL.Google Scholar], but RIC should still be considered a suitable alternative for ineligible patients. The development of new RIC regimens may bolster potent antileukemic effects and maintain safety, and advances in MAC may result in safer regimens that allow more patients to be considered for this approach [26Shimoni A. Shem-Tov N. Volchek Y. Danylesko I. Yerushalmi R. Nagler A. Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity.Bone Marrow Transplant. 2012; 47: 1274-1282Crossref PubMed Scopus (35) Google Scholar]. A lower incidence of GVHD has been described in patients who receive RIC prior to allogeneic HCT. Despite this difference, the graft-versus-leukemia (GVL) effect remains potent, and these patients achieve superior long-term disease control compared with those receiving chemotherapy or immunochemotherapy alone [20Aoudjhane M. Labopin M. Gorin N.C. et al.Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT).Leukemia. 2005; 19: 2304-2312Crossref PubMed Scopus (377) Google Scholar, 21Luger S.M. Ringdén O. Zhang M.J. et al.Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDS.Bone Marrow Transplant. 2012; 47: 203-211Crossref PubMed Scopus (212) Google Scholar]. A large body of evidence links GVHD and GVL as two complementary, inseparable processes that provide both benefit and harm to this population of patients. Despite unfolding simultaneously, they are not tightly linked, and the severity of GVHD-mediated end organ damage is not proportional to the GVL effect [27Lee S.J. Klein J.P. Barrett A.J. et al.Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse.Blood. 2002; 100: 406-414Crossref PubMed Scopus (425) Google Scholar]. Clinicians and investigators have identified GVHD as a significant driver of morbidity and mortality and, over the years, have invested immense time and resources to better understand the mechanisms and risk factors underlying these processes. Apart from MAC regimens, a number of risk factors exist for aGVHD. These include peripheral blood stem cell (PBSC) grafts, allografting an unrelated donor, advanced age, KPS <90%, total body irradiation (TBI)-based preparative regimens, and others [28Gale R.P. Bortin M.M. van Bekkum D.W. et al.Risk factors for acute graft-versus-host disease.Br J Haematol. 1987; 67: 397-406Crossref PubMed Scopus (277) Google Scholar, 29Weisdorf D. Hakke R. Blazar B. et al.Risk factors for acute graft-versus-host disease in histocompatible donor bone marrow transplantation.Transplantation. 1991; 51: 1197-1203Crossref PubMed Scopus (234) Google Scholar, 30Nash R.A. Pepe M.S. Storb R. et al.Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate.Blood. 1992; 80: 1838-1845Crossref PubMed Google Scholar, 31Przepiorka D. Smith T.L. Folloder J. et al.Risk factors for acute graft-versus-host disease after allogeneic blood stem cell transplantation.Blood. 1999; 94: 1465-1470Crossref PubMed Google Scholar, 32Hahn T. McCarthy P.L. Zhang M.J. et al.Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia.J Clin Oncol. 2008; 26: 5728-5734Crossref PubMed Scopus (139) Google Scholar, 33Jagasia M. Arora M. Flowers M.E. et al.Risk factors for acute GVHD and survival after hematopoietic cell transplantation.Blood. 2012; 119: 296-307Crossref PubMed Scopus (401) Google Scholar, 34Lee S.E. Cho B.S. Kim J.H. et al.Risk and prognostic factors for acute GVHD based on NIH consensus criteria.Bone Marrow Transplant. 2013; 48: 587-592Crossref PubMed Scopus (49) Google Scholar]. Importantly, aGVHD is a risk factor for chronic GVHD (cGVHD), and there is substantial overlap between the risks for both forms of GVHD. Older patients, those who receive PBSC grafts, the use of human leukocyte antigen (HLA)-mismatched or unrelated donors, TBI-based conditioning regimens, and several others are established risks for cGVHD [35Remberger M. Kumlien G. Aschan J. et al.Risk factors for moderate-to-severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.Biol Blood Marrow Transplant. 2002; 8: 674-682Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 36Carlens S. Ringdén O. Remberger M. et al.Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis.Bone Marrow Transplant. 1998; 22: 755-761Crossref PubMed Scopus (163) Google Scholar, 37Flowers M.E. Inamoto Y. Carpenter P.A. et al.Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria.Blood. 2011; 117: 3214-3219Crossref PubMed Scopus (417) Google Scholar, 38Atkinson K. Horowitz M.M. Gale R.P. et al.Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation.Blood. 1990; 75: 2459-2464PubMed Google Scholar]. The sequelae of both aGVHD and cGVHD and their impact on clinical outcomes are well documented in the medical literature [39Storb R. Gyurkocza B. Storer B.E. et al.Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation.J Clin Oncol. 2013; 31: 1530-1538Crossref PubMed Scopus (161) Google Scholar, 40Pidala J. Kim J. Anasetti C. et al.The global severity of chronic graft-versus-host disease, determined by National Institutes of Health consensus criteria, is associated with overall survival and non-relapse mortality.Haematologica. 2011; 96: 1678-1684Crossref PubMed Scopus (46) Google Scholar, 41Gustafsson Jernberg A. Remberger M. Ringdén O. Winiarski J. Graft-versus-leukaemia effect in children: chronic GVHD has a significant impact on relapse and survival.Bone Marrow Transplant. 2003; 31: 175-181Crossref PubMed Scopus (58) Google Scholar]. Patients with cGVHD face significant long-term complications that are associated with a diminished quality of life, mental health challenges, increased healthcare expenditures, and late deaths [42Lee S.J. Kim H.T. Ho V.T. et al.Quality of life associated with acute and chronic graft-versus-host disease.Bone Marrow Transplant. 2006; 38: 305-310Crossref PubMed Scopus (162) Google Scholar, 43Svahn B.M. Remberger M. Alvin O. Karlsson H. Ringdén O. Increased costs after allogeneic haematopoietic SCT are associated with major complications and re-transplantation.Bone Marrow Transplant. 2012; 47: 706-715Crossref PubMed Scopus (34) Google Scholar, 44Khera N. Emmert A. Storer B.E. Sandmaier B.M. Alyea E.P. Lee S.J. Costs of allogeneic hematopoietic cell transplantation using reduced intensity conditioning regimens.Oncologist. 2014; 19: 639-644Crossref PubMed Scopus (26) Google Scholar, 45Wingard J.R. Majhail N.S. Brazauskas R. et al.Long-term survival and late deaths after allogeneic hematopoietic cell transplantation.J Clin Oncol. 2011; 29: 2230-2239Crossref PubMed Scopus (413) Google Scholar, 46Fraser C.J. Bhatia S. Ness K. et al.Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study.Blood. 2006; 108: 2867-2873Crossref PubMed Scopus (209) Google Scholar]. These long-term sequelae are compounded by the toxicities of glucocorticoids, calcineurin inhibitors, and other agents that are used for disease control. Infectious complications are commonplace and are a direct manifestation of a biologically altered immune system. Patients with cGVHD have defects in both humoral and cellular immunity evidenced by high rates of dysgammaglobulinemia, distorted B-cell homeostasis with reduced quantities of CD19+ B cells, and high B-cell-activating factor (BAFF) to B-cell ratios. Importantly, low levels of the IgG subclasses IgG2 and IgG4 increase these patients' susceptibility to infections, particularly with encapsulated organisms [47Kuzmina Z. Greinix H.T. Weigl R. et al.Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease-associated dysgammaglobulinemia.Blood. 2011; 117: 2265-2274Crossref PubMed Scopus (77) Google Scholar, 48Aucouturier P. Barra A. Intrator L. et al.Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.Blood. 1987; 70: 779-785Crossref PubMed Google Scholar, 49Kulkarni S. Powles R. Treleaven J. et al.Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants.Blood. 2000; 95: 3683-3686Crossref PubMed Google Scholar]. Furthermore, cGVHD-mediated defects in cellular immunity lead to susceptibility to viral infections, reactivation of dormant viruses, and a variety of other infectious perils [50Fry T.J. Mackall C.L. Immune reconstitution following hematopoietic progenitor cell transplantation: challenges for the future.Bone Marrow Transplant. 2005; 35: S53-S57Crossref PubMed Scopus (53) Google Scholar]. Outside of this immune dysfunction, late risks of cGVHD include an increased risk of coronary artery and cerebrovascular disease. This is likely an interplay between elevated levels of circulating cytokines secondary to GVHD, the effects of corticosteroids and/or calcineurin inhibitors on lipid metabolism, or a combination of these risks [51Griffith M.L. Savani B.N. Boord J.B. Dyslipidemia after allogeneic hematopoietic stem cell transplantation: evaluation and management.Blood. 2010; 116: 1197-1204Crossref PubMed Scopus (53) Google Scholar]. Aggressive risk factor reduction, including tight glycemic control, management of lipids, and the prompt initiation of antihypertensive therapy is necessary in order to mitigate harm. Endocrine disorders, including osteopenia/osteoporosis and thyroid failure, complicate a substantial percentage of these patients' posttransplantation courses [52Stern J.M. Chesnut C.H. Bruemmer B. et al.Bone density loss during treatment of chronic GVHD.Bone Marrow Transplant. 1996; 17: 395-400PubMed Google Scholar, 53Tauchmanovà L. Colao A. Lombardi G. Rotoli B. Selleri C. Bone loss and its management in long-term survivors from allogeneic stem cell transplantation.J Clin Endocrinol Metab. 2007; 92: 4536-4545Crossref PubMed Scopus (46) Google Scholar, 54Savani B.N. Labopin M. Blaise D. et al.Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT.Haematologica. 2016; 101: 256-262Crossref PubMed Scopus (35) Google Scholar]. Furthermore, chronic kidney disease is a relatively common, late manifestation of cGVHD. Ocular and genitourinary complications are widely seen and are described extensively in the medical literature [55Abboud I. Peraldi M.N. Hingorani S. Chronic kidney diseases in long-term survivors after allogeneic hematopoietic stem cell transplantation: monitoring and management guidelines.Semin Hematol. 2012; 49: 73-82Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar, 56Socié G. Salooja N. Cohen A. et al.Nonmalignant late effects after allogeneic stem cell transplantation.Blood. 2003; 101: 3373-3385Crossref PubMed Scopus (328) Google Scholar, 57Spinelli S. Chiodi S. Costantini S. et al.Female genital tract graft-versus-host disease following allogeneic bone marrow transplantation.Haematologica. 2003; 88: 1163-1168PubMed Google Scholar, 58Wong F.L. Francisco L. Togawa K. et al.Longitudinal trajectory of sexual functioning after hematopoietic cell transplantation: impact of chronic graft-versus-host disease and total body irradiation.Blood. 2013; 122: 3973-3981Crossref PubMed Scopus (27) Google Scholar]. Bronchiolitis obliterans is associated with a high morbidity and mortality in the postallogeneic HCT period and may also be considered a late complication of cGVHD. Risk factors for this disease include cGVHD, PBSC grafts, and ABO mismatch [59Ditschkowski M. Elmaagacli A.H. Koldehoff M. Gromke T. Trenschel R. Beelen D.W. Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight–new perspectives?.Bone Marrow Transplant. 2013; 48: 1224-1229Crossref PubMed Scopus (30) Google Scholar]. Finally, 2.2–6.1% of post-HCT patients develop secondary malignancies within 10 years of HCT [60Shimoni A. Shem-Tov N. Chetrit A. et al.Secondary malignancies after allogeneic stem-cell transplantation in the era of reduced-intensity conditioning; the incidence is not reduced.Leukemia. 2013; 27: 829-835Crossref PubMed Scopus (45) Google Scholar]. Among patients with cGVHD, cancers of the skin and buccal mucosa are the most common [61Curtis R.E. Rowlings P.A. Deeg H.J. et al.Solid cancers after bone marrow transplantation.N Engl J Med. 1997; 336: 897-904Crossref PubMed Scopus (755) Google Scholar, 62Bhatia S. Louie A.D. Bhatia R. et al.Solid cancers after bone marrow transplantation.J Clin Oncol. 2001; 19: 464-471Crossref PubMed Scopus (249) Google Scholar]. The late effects of cGVHD are summarized in Table 1.Table 1Summary of the late effects of cGVHDSite/Organ systemDysfunctionManifestationImmuneDysgammaglobulinemia, defects in humoral immunity, defects in cellular immunityBacterial and viral infections, opportunistic infectionsCardiovascularAtherosclerosis, hyperlipidemiaCoronary artery disease, cerebrovascular diseasePulmonaryBronchiolitis obliterans syndromeDecreased FEV1 and FEV1/FVC ratio of <0.7 on PFTEndocrineDiabetes mellitus, thyroid failure, male hypogonadismHyperglycemia, sequelae of hypothyroidism and hypogonadismMusculoskeletalAvascular necrosis, osteopenia/osteoporosisReduced bone density on DEXA scanning, low vitamin D levelRenalChronic kidney diseaseDecline in glomerular filtration rate not attributable to another etiologyOphthalmologiccGVHDDry eyesPsychologicalChallenges with mental health and anxietyReduced scores on self-reporting surveysMalignanciesSecondary neoplasmsPredominantly squamous cell carcinomas (skin and buccal mucosa)cGVHD = chronic graft-versus-host disease; DEXA = dual-energy X-ray absorptiometry; FEV1 = forced expiratory volume in one second; FVC = forced vital capacity; PFTs = pulmonary function test. Open table in a new tab cGVHD = chronic graft-versus-ho" @default.
• W2336931112 created "2016-06-24" @default.
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• W2336931112 title "Peripheral blood stem cell versus bone marrow transplantation: A perspective from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation" @default.
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