Hematopoietic Cell Transplantation In Older Patients Research Articles

Practice Patterns of Allogeneic Hematopoietic Cell Transplantation (HCT) for Adults with Acute Lymphoblastic Leukemia (ALL)

Introduction:HCT is a valuable therapeutic modality in ALL. Though controversial in standard-risk ALL, particularly those who are treated with pediatric chemotherapy regimen, HCT is still considered to be the standard of care in high-risk patients such as Philadelphia chromosome positive ALL. Variations exist in the utilization of HCT across the centers. In this context, we sought to evaluate practice patterns of HCT in ALL patients using a large national database.Methods:We utilized the National Cancer Database (NCDB) Participant User File to extract patient-level data of adult patients (aged 18-80 years) diagnosed with ALL between 2003-2012. Patients with unknown HCT or chemotherapy status and those who did not receive chemotherapy were excluded. Only patients treated in the reporting facility were included. Data abstracted include age, sex, race, income, insurance, educational status, and HCT. Specific chemotherapy regimen, molecular data and data regarding minimal residual disease were not available in NCDB. Multivariate logistic regression analysis was performed to determine variables associated with the use of HCT.Results:Of 11,871 patients included in the study, 1502 patients (12.7%) received HCT. Patients who did versus did not receive HCT were more likely to be younger (median age 42 vs. 47 years; p <0.001), female (p<0.01), Caucasian (p<0.0001), treated at an academic facility (p <0.001), have higher educational status (p=0.001), higher income status (p <0.001), private insurance (p<0.0001) and lower Charlson comorbidity scores (p=0.001). In a multivariate analysis, age >60 years, male sex, higher Charlson comorbidity score, treatment at a non-academic center, poor educational status and Medicare/Medicaid insurance or uninsured status were associated with a significantly lower likelihood of receiving HCT (Table 1). Race and income status did not influence receipt of HCT.Conclusion:Our large study demonstrates variations in the HCT practices in ALL patients based on biological and non-biological factors. While a lower use of HCT in older patients or those with higher comorbidities is expected, variations based on facility type, insurance, educational status, and to some extent, gender may indicate a possibility of health care disparity based on socioeconomic and health system factors. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years

Numbers of Hematopoietic cell transplantation (HCT) in Europe and collaborating countries continues to rise with 48,512 HCT in 43,581 patients, comprising of 19,798 (41%) allogeneic and 28,714 (59%) autologous, reported by 700 centers in 51 countries during 2019. Main indications were myeloid malignancies 10,764 (25%), lymphoid malignancies 27,895 (64%), and nonmalignant disorders 3173 (7%). A marked growth in CAR-T cellular therapies from 151 in 2017 to 1134 patients in 2019 is observed. This year’s analyses focus on changes over 30 years. Since the first survey in 1990 where 143 centers reported 4234 HCT, the number has increased to 700 centers and 48,512 HCT. Transplants were reported in 20 countries in 1990, and 51, 30 years later. More than 800,000 HCT in 715,000 patients were reported overall. Next to the massive expansion of HCT technology, most notable developments include the success of unrelated donor and haploidentical HCT, an increase followed by decrease in the number of cord blood transplants, use of reduced intensity HCT in older patients, and the phenomenal rise in cellular therapy. This annual report of the European Society for Blood and Marrow Transplantation (EBMT) reflects current activity and highlights important trends vital for health care planning.

High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia

High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Personalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not Related to the Radiation Dose Delivered

Personalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not Related to the Radiation Dose Delivered

Access and Referral Barriers to Autologous and Allogeneic Hematopoietic Cell Transplantation in Adult Patients with Cancer: A Systematic Review with a Specific Focus on Geriatric Population

Introduction:Hematopoietic cell transplantation (HCT) advances in reduced intensity conditioning, donor identification, and supportive care have led to its increased use over the last few decades. HCT is a complex process that requires coordination at multiple levels, and there may be disparities in its utilization. To better understand these access disparities, we conducted a systematic review of studies that assessed barriers to referral and/or receipt of HCT. Additionally, we focused on a subgroup of older patients (aged ≥65 at transplant), who we hypothesized would be at higher risk for access barriers to HCT.Methods:A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for articles published in English from PubMed, Embase, Cumulative Index for Nursing and Allied Health, and Cochrane Central Register of Controlled Trials between the database inception and January 12th, 2018. Inclusion criteria were: 1) clinical trials, observational, qualitative, cross-sectional, or mixed-method study designs; 2) study assessed barriers to HCT or factors associated with referral for or receipt of HCT (except for country-specific economic factors as these are less likely to be targetable), 3) included patients ≥18 years with cancer. Narrative review articles and abstracts without full text were excluded. Two authors independently reviewed all titles and abstracts (N=3,262) and assessed studies for full-text eligibility (N=153). A third reviewer resolved any discrepancies. Eighteen studies met eligibility criteria and an additional 5 studies (not identified on our search strategy) were included on review of the bibliographies. Literature on subgroup of patients aged ≥65 was also assessed.Results:Among the 23 studies included, 16 were published after 2010. Studies were retrospective (N=18; 14 from registry data), cross-sectional (N=4; 2 from registry data), and mixed-method (N=1), and primarily conducted in the US (N=21). Barriers were assessed at the patient level (N=19; sample size ranged from 350 to 38,420), healthcare professional level (N=3; 1 study assessed both patients and healthcare professionals), or country level (N=2). Fourteen studies included some information on age of the patients and 10 studies included some patients aged 60 and above. Seventeen studies only included patients with hematologic malignancies. Age was the most common barrier identified (N=16 out of 16 studies identified older age as a barrier). Fourteen studies showed that older age was associated with lower odds of referral for or receipt of HCT, and the remaining 2 studies provided descriptive data showing lower percentages of patients receiving HCT compared to the younger age groups. Table 1 shows other potential barriers or factors associated with lower referral for or receipt of HCT at the patient, disease, physician, and organizational levels. These included race (N=14 out of 16 studies identified non-white race as a barrier), insurance or financial capacity (N=11/12), comorbidity (N=8/9), gender (N=7/17; primarily female), disease status (N=5/5), patient preferences (N=5/5), time of diagnosis (N=5/5), cancer type (N=4/6), and socioeconomic status (N=4/5). Only one study evaluated factors associated with receipt of HCT in a subgroup of patients ≥65 years. Older age, female gender, and a diagnosis of leukemia other than acute myeloid leukemia were associated with lower odds of receiving HCT.Conclusions:There are limited prospective studies evaluating access barriers to HCT in adult patients with cancer. Older age is the most commonly reported barrier to both autologous and allogeneic HCT, although studies have not addressed specific mechanisms for this disparity. In addition, other potential barriers identified such as gender, race, insurance status, and comorbidity have not been well studied in the context of older age. While some barriers may be difficult to intervene upon (e.g. comorbidity, disease status, performance status), many are amenable to interventions (e.g. socioeconomic status, distance to transplant center, social support). With the increasing trend for HCT in older patients, there is a critical need for prospective studies that better describe these access barriers and their mechanisms in order to design future interventions to reduce disparities in HCT access. [Display omitted] DisclosuresLiesveld:Onconova: Other: DSMB; Abbvie: Honoraria. Aljitawi:Medpace: Consultancy; The University of Rochester Medical Center: Patents & Royalties: Pending patent related to decellularized Wharton's jelly matrix. Klepin:Genentech Inc: Consultancy. Stock:Jazz Pharmaceuticals: Consultancy. Wildes:Janssen: Research Funding. Majhail:Incyte: Honoraria; Anthem, Inc.: Consultancy; Atara: Honoraria.

Socioeconomic and health system factors associated with lower utilization of hematopoietic cell transplantation in older patients with acute myeloid leukemia.

Receipt of hematopoietic cell transplantation (HCT) can improve overall survival in older patients with intermediate or high-risk acute myeloid leukemia (AML); however, utilization of HCT is poor. It is important to understand the factors that affect the receipt of HCT in a real-world setting among the older patients. We utilized the National Cancer Database to determine receipt of HCT in older patients (61-75 years) with intermediate or high-risk AML reported between 2003 and 2012. Multivariate logistic regression analysis was used to determine factors associated with receipt of HCT. Only 5.5% of older patients (n = 17,555) underwent HCT. Factors associated with a lower likelihood of receiving HCT included receipt of care in a non-academic hospital, race other than white, older age, Charlson comorbidity score of ≥1, uninsured status, Medicaid or Medicare insurance, and lower educational status. The receipt of HCT in older patients is low and varies based on biological as well as non-biologic factors, such as hospital type, insurance, and educational status. Nationwide efforts to improve access to HCT for appropriate patients are necessary.

Survival Following Allogeneic Hematopoietic Cell Transplantation in Older High-Risk Acute Myeloid Leukemia Patients Initially Treated with CPX-351 Liposome Injection Versus Standard Cytarabine and Daunorubicin: Subgroup Analysis of a Large Phase III Trial

Introduction Intensive induction chemotherapy for acute myeloid leukemia (AML) in patients aged 60 years or older has lower remission rates with increased induction mortality compared with younger patients. CPX-351 (Vyxeos) is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio. Previously reported results from a phase III, randomized, open-label study of CPX-351 versus 7+3 (cytarabine and daunorubicin) in newly diagnosed older patients with secondary AML suggested superior survival in those randomized to CPX-351. We conducted an exploratory analysis of patients who received allogeneic hematopoietic cell transplantation (HCT) after induction treatment, to determine the effect of HCT on outcome by arm, as few patients in this age range can be cured with chemotherapy alone. Methods This phase III trial was a randomized, open-label, parallel-arm, standard therapy-controlled study. Eligible patients were aged 60 to 75 years with newly diagnosed secondary AML defined as having a history of prior cytotoxic treatment, antecedent myelodysplastic syndrome (MDS) (± prior treatment with hypomethylating agents), or AML with World Health Organization-defined MDS-related cytogenetic abnormalities. Patients were randomized 1:1 to CPX-351 induction (100 units/m2 [100 mg/m2 cytarabine + 44 mg daunorubicin mg/m2] on days 1, 3, and 5 [first induction only]) or 7+3 induction (cytarabine 100 mg/m2/day x 7 days plus daunorubicin 60 mg/m2 on days 1, 2, and 3 [first induction] or x 5 days [reinduction/consolidation] plus daunorubicin 60 mg/m2 on days 1 and 2). The distribution of overall survival (OS) after HCT in each treatment arm was estimated using the Kaplan-Meier method, and Cox regression hazard ratio and OS rates, along with corresponding confidence intervals, are reported. Results Three hundred and nine (309) patients were enrolled from December 2012 to November 2014 at 39 US and Canadian sites, with 153 patients randomized to the CPX-351 arm and 156 to the 7+3 arm. Patients in either arm responding to induction with a complete response (CR) or a CR with incomplete platelet or neutrophil recovery (n=125) were considered for allogeneic HCT when possible. In total, 91 patients were transplanted: 52 (34%) from the CPX-351 arm and 39 (25%) from the 7+3 arm. Patient and AML characteristics were similar according to randomized arm, including percentage of patients in each arm that underwent transplant in CR/CRi status (Table); however, the CPX-351 arm contained a higher percentage of older patients (age ≥ 70) who were transplanted (CPX-351, 31%; 7+3, 15%). Mortality at 100 days after transplant was 9.6% for patients in the CPX-351 arm and 20.5% in the 7+3 arm patients. Causes of death Conclusions An exploratory analysis from this phase III study demonstrated that CPX-351, compared with standard cytarabine and daunorubicin, resulted in better outcomes after allogeneic HCT in older patients with high-risk AML, including 53% fewer deaths within 100 days of transplant. These results suggest that CPX-351 may provide an effective bridge to successful transplant for a very poor-risk subgroup of AML patients. Support: Celator Pharmaceuticals, Inc., a subsidiary of Jazz Pharmaceuticals plc. Disclosures Uy:Boehringer Ingelheim: Consultancy; Glycomimetics: Consultancy. Cortes:ARIAD: Consultancy, Research Funding; Bristol-Myers Squib: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Ritchie:Astellas Pharma: Research Funding; Ariad: Speakers Bureau; Celgene: Consultancy, Other: Travel, Accomodations, Expenses, Speakers Bureau; Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; NS Pharma: Research Funding; Bristol-Meyers Squibb: Research Funding. Stuart:Celator: Research Funding; Incyte: Research Funding; Astellas: Research Funding; Sunesis: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding; Agios: Research Funding; Bayer: Research Funding. Strickland:Alexion Pharmaceuticals: Consultancy; Ambit: Consultancy; Baxalta: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; CTI Biopharma: Consultancy; Daiichi Sankyo: Consultancy; Sunesis Pharmaceuticals: Consultancy, Research Funding; Abbvie: Research Funding; Astellas Pharma: Research Funding; Celator: Research Funding; Cyclacel: Research Funding; GlaxoSmithKline: Research Funding; Karyopharm Therapeutica: Research Funding; Sanofi: Research Funding. Hogge:Sanofi: Consultancy; Roche: Other: Travel, Accomodations, Expenses. Stone:Sunesis Pharmaceuticals: Consultancy; Xenetic Biosciences: Consultancy; Agios: Consultancy; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Celator: Consultancy; Roche: Consultancy; Seattle Genetics: Consultancy; Juno Therapeutics: Consultancy; Jansen: Consultancy; Merck: Consultancy; ONO: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy. Kolitz:Gliead Sciences: Consultancy; Pharmacyclics: Consultancy; Seattle Genetics: Consultancy. Schiller:Celator: Research Funding. Ryan:AbbVie: Equity Ownership; U of Rochester: Patents & Royalties. Chiarella:Celator Pharmaceuticals, Inc., a subsidiary of Jazz Pharmaceuticals plc.: Employment, Equity Ownership. Louie:Celator Pharmaceuticals, Inc., a subsidiary of Jazz Pharmaceuticals plc.: Employment, Equity Ownership. Medeiros:MEI Pharma: Research Funding; Merck/Schering Plough: Research Funding; Celgene: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; ARIAD: Consultancy; Celator: Other: Travel, Accomodations, Expenses, Research Funding; Roche/Genentech: Consultancy, Research Funding; Pfizer: Consultancy; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Amgen: Consultancy.

Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials.

Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2014

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) was chartered by the National Heart, Lung, and Blood Institute and the National Cancer Institute(NCI) in 2001 to conduct clinical trials aimed at improving the outcome of patients undergoing hematopoietic cell transplantation (HCT). Since its inception, activities of the BMT CTN have been guided by a series of State of the Science Symposia (SOSS), conducted to determine the most important and clinically relevant questions to be addressed by the cooperative activities of the Network. The first State of the Science Symposium identified 6 major questions that the BMT CTN should consider (see Table 1). Over the following 6 years, the BMT CTN activated 12 trials that addressed most of these questions, as well as others, and accrued more than 2000 patients to these trials. In 2007, a second SOSS (SOSS2) identified a new series of 11 clinically important questions (see Table 1) [1]. Since SOSS2, the BMT CTN has developed and activated 7 studies addressing these issues, 6 of which have completed accrual; accrual continues to the remaining study. The NCI cancer cooperative groups developed and activated 2 additional trials endorsed by the BMT CTN addressing these questions,1 of which has completed accrual with 1 ongoing. Studies addressing the final 2 SOSS2 questions were not initiated after further analysis determined that they were likely not feasible at this time. Overall, the BMT CTN has activated 33 trials addressing many of the most pressing questions facing the HCT community, has accrued >6700 patients to trials, and has published results in 37 manuscripts, including many high-impact, practice-changing papers [2]. Table 1 Clinical Research Questions Identified at SOSS The BMT CTN held its third SOSS meeting in February 2014 to set a scientific agenda for the coming half decade. Given the success of the previous 2 SOSS meetings, the 2014 SOSS followed a similar format. Briefly, approximately 9 months before the meeting, a BMT CTN planning group formed 13 committees (similar to those in SOSS2) addressing 13 major topics in HCT, and the planning group named committee chairs and members for each committee. Committee members included cooperative group leaders, representatives from specialized programs of research excellence, individual cancer center leaders, and laboratory-oriented investigators and clinical trialists. To encourage diverse views and gain the broadest possible perspective, no individual was permitted to serve on more than 1 committee. Additionally, 2 external reviewers, who were not active participants in BMT CTN activities or centers, were identified for each committee. The planning group, committee chairs, members, and external reviewers are listed in Table 2. Each committee was charged with identifying up to 3 of the most important clinical questions in their area that could be addressed by the BMT CTN in the next few years. The committees met multiple times over the ensuing 6 months to develop their list and to create brief documents describing the outcomes of their deliberations. These reports were circulated to the SOSS planning group, the other committee chairs, and the external reviewers before the SOSS meeting. Participation in the SOSS meeting was open to the public and approximately 350 individuals attended. At the meeting, each committee chair presented his or her group’s report, following which the external reviewers presented their views. A discussion period followed each presentation; these discussions were open to all in attendance. At the conclusion of the public meeting, the planning committee, committee chairs, and external reviewers met, modified, and prioritized the study concepts, based on the SOSS meeting discussions. This article summarizes the individual committee reports and a list of those trials most enthusiastically endorsed by the symposium leadership. Table 2 BMT CTN SOSS Committees and Reviewers COMMITTEE 1: LEUKEMIA Current State of the Science Leukemia is the most common indication for allogeneic HCT and disease recurrence is the most common reason for transplantation failure. Relapse occurs most frequently early after transplantation before full donor immune reactivity has occurred. Accordingly, this committee chose to focus primarily on strategies to mitigate the risk of relapse in acute myeloid leukemia (AML) after HCT based on the availability of new agents, encouraging preliminary data, and trial feasibility. The committee also noted that the role of allogeneic HCT in older patients remains unsettled. Strategy 1: A Randomized, Double-blind, Phase III Study of Fms-like tyrosine Kinase 3 (FLT3) Inhibition Compared with Placebo as Maintenance Therapy in Subjects with FLT3–internal Tandem Duplication (ITD)+ AML Who Are in Remission after Allogeneic HCT Hypothesis The continued administration of FLT3 inhibition in patients with FLT3-ITD+ AML in remission after HCT is feasible and will prevent early relapse leading to improved leukemia-free survival compared with placebo.

Allogeneic Hematopoietic Cell Transplantation in Septuagenarians

Allogeneic Hematopoietic Cell Transplantation in Septuagenarians

Reduced-intensity conditioning transplantation in myeloid malignancies

The development of non-myeloablative and reduced-intensity conditioning regimens has enabled older or medically infirm patients with myeloid malignancies to be treated with allogeneic hematopoietic cell transplantation (HCT). The regimens are sufficiently immunosuppressive to allow engraftment of allogeneic cells and they rely largely on graft-versus-leukemia effects rather than high-dose cytotoxic therapy to eliminate malignant cells. Overall 2-5-year survivals after allogeneic HCT in older patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) have ranged from 25% to 64%. Outcomes were comparable for human leukocyte antigen-matched related and unrelated grafts. The best results were seen in patients transplanted in the first or second remission. Relapse and progressive disease continue to be problems, particularly in patients with large tumor burdens at the time of HCT. Reduction of the tumor burden before HCT with targeted therapy such as radiolabelled anti-CD45 antibody may improve the outcome. Despite still existing problems, early results in elderly patients with AML/MDS have been encouraging.

Non-Myeloablative Hematopoietic Stem Cell Transplantation in Older Patients with AML and MDS: Results from the Center for International Blood and Marrow Transplant Research (CIBMTR)

Background: AML and MDS disproportionately affect older-aged individuals. Hematopoietic cell transplantation (HCT) is the best established curative therapy but is generally not offered due to concerns about toxicity and poor outcome. Reduced-intensity conditioning (RIC) regimens have been developed to allow allografting in older patients; however, there is a paucity of data to support transplantation in patients over 65 years of age.Purpose: To better study age as a predictor of outcome, we retrospectively analyzed data reported to the CIBMTR from 1995–2005 among patients receiving RIC HCT for MDS (551 patients) and AML (565 patients) in first complete remission (CR).Patient and Methods: Outcomes analyzed for both disease groups included transplant-related mortality (TRM), engraftment, incidence of acute and chronic graft-versus-host disease (GVHD), leukemia-free (LFS) and overall survival (OS). Patients were stratified according to age cohorts for comparison: 40–54, 54–59, 60–64 and ≥65 years.Results: Clinical characteristics were well matched across age cohorts but notably, most AML patients presented with de novo disease (P=0.001) and received their allograft from a matched related donor (MRD) (P=0.001) with 51% of patients ≥65 years having a MRD. MDS patients more often had unrelated donors (URD), especially in the older cohorts (73% for ≥ 65 years); but donor type was not significantly different between groups. Most patients received peripheral blood (PB) allografts (76–97%), fludarabine-containing regimens for conditioning and cyclosporine-containing regimens for GVHD prophylaxis. Univariate analysis demonstrated no statistically significant differences in TRM across age cohorts and no overall difference in occurrence of acute (31–35% at 100 days) or chronic GVHD (36–53% at 2 years). Relapse rates were similar across all age groups (29–39% at 3 years) (Table). Multivariate analysis revealed no statistically significant impact of age on TRM, relapse, LFS, or OS (all p > 0.4). Disease and status at transplant were significant risk factors for OS/LFS at 1 year while affecting TRM/relapse at 2 years. Performance status and HLA disparity were also significant at 2 years for nearly all outcomes.Conclusion: 1. The outcomes for older adults undergoing allogeneic HCT are not significantly different than for younger adults, even after adjusting for multiple risk factors; 2. Age by itself should not be the limiting factor for proceeding to allogeneic HCT in older patients with AML or MDS; 3. Continued participation in clinical trials should be encouraged to explore strategies that could improve treatment outcome.Univariate probabilities of patients age ≥40 years receiving allogeneic HCT for AML/MDS in first complete remission reported to the CIBMTR, 1995–2005.N40–54N55–60N60–64N>65AMLTRM22015013263100 days11 (7–16)%6 (3–10)%13 (8–20)%10 (4–18)%1 year20 (15–26)%18 (12–24)%24 (17–33)%30 (19–42)%Relapse1 year27 (21–33)%34 (26–42)%31 (23–40)%22 (12–33)%3 years32 (26–39)%35 (27–43)%39 (30–49)%33 (21–46)%LFS1 year53 (46–60)%49 (41–58)%44 (35–53)%48 (36–61)%3 years43 (36–51)%41 (32–50)%27 (19–37)%34 (22–47)%OS100 days84 (78–88)%92 (87–96)%83 (76–89)%89 (80–95)%1 year59 (52–65)%60 (52–68)%51 (42–60)%51 (39–64)%3 years45 (40–54)%47 (42–59)%30 (25–43)%36(24–49)%Follow-up (months)37 (2–110)25 (1–87)36 (3–96)29 (3–59)MDSTRM21915012755100 days17 (13–23)%17 (11–23)%14 (9–21)%19 (9–30)%1 year31 (24–37)%33 (25–41)%32 (24–41)%34 (22–47)%Relapse1 year26 (20–32)%27 (20–35)%26 (18–34)%25 (14–37)%3 years29 (23–35)%29 (22–37)%31 (23–40)% higher33 (20–47)%LFS1 year43 (36–50)%40 (32–49)%43 (34–51)%42 (29–56)%3 years36 (29–43)%27 (–2035)%29 (21–39)%23 (12–38)%OS100 days77 (71–82)%77 (70–83)%81 (74–87)%76 (64–87)%1 year50 (43–56)%46 (38–54)%53 (44–62)%48 (35–61)%3 years39 (32–46)%29 (22–37)%30 (21–40)%29 (17–43)%Follow-up (months)36 (2–86)40 (3–86)35 (3–68)36 (3–85)

Outcome of Allogeneic Hematopoietic Cell Transplantation (HCT) for Patients with Severe Aplastic Anemia (SAA) above the Age of 40 Years.

Allogeneic HCT for SAA is definitive curative therapy for this otherwise fatal hematologic disease. For younger SAA patients, long-term survival of approximately 90% can be expected after HCT from HLA-identical siblings with cyclophosphamide/ antithymocyte globulin (CY/ATG) conditioning and post-grafting methotrexate/cyclosporine (MTX/CSP) immunosuppression. Most transplant center guidelines and many published reports restrict allogeneic HCT to SAA patients under the age of 40 years, due to concern of increased morbidity and mortality from HCT in older patients. We reviewed the clinical records of all 20 patients with a diagnosis of SAA who were treated with HCT from an HLA-identical sibling at the Fred Hutchinson Cancer Research Center from July 1988 to January 2006 and were above the age of 40 years at the time of HCT. The conditioning regimen consisted of CY/ATG for all but 2 patients who did not receive ATG. MTX and CSP were used as post grafting immunosuppression. The median age of the 10 men and 10 women was 47 (40–63) years. The median time from diagnosis to HCT was 2.7 (0.8–48.5) months. Ten patients had previously received immunosuppressive treatment and all 20 patients had received multiple red blood cell and platelet transfusions before HCT. The median follow-up of surviving patients was 86 (range, 17–194) months after HCT. One patient had graft rejection on day 28 and is alive and well following reconditioning and repeat marrow grafting from original donor. The incidence of acute grades II and III graft-versus-host-disease (GVHD) was 41% and 6%, respectively, the incidence of chronic GVHD (cGVHD) was 37% (6 patients). Overall survival was 70% (fig. 1). Three patients died before engraftment: from preexisting disseminated aspergillosis (n=1), congestive heart failure likely related to CY toxicity (n=1) and preexisting disseminated candidiasis (n=1) on days 2, 3 and 6, respectively. Three patients died from infections on days 83, 179 and 223; in the latter 2 cases, the infections were related to cGVHD and its treatment. The median time to discontinuation of immune suppression was 6 (range, 6–46) months (fig. 1). At last follow-up, 2 patients remain on immune suppression for treatment of cGVHD at 24 and 41 months, respectively. Three patients experienced avascular joint necroses 3, 6 and 9 years after HCT; they had cGVHD (n=2) and/or received extensive steroid treatment before HCT (n=2). Two patients developed superficial basal cell carcinoma at 5.5 and 15 years after HCT. Our data suggest that allogeneic HCT from sibling donor can be successfully extended to SAA patients older than 40 years. Although the number of patients are limited, survival after HLA-identical sibling HCT appears superior to published results of immune suppression therapy for patients >40 years of age. Pre-HCT cardiac screening is indicated to minimize the risk of conditioning related toxicity. Improved treatment to effectively treat or prevent cGVHD and associated infections remain important issues. [Display omitted]