Allogeneic hematopoietic cell transplantation in patients ⩾70 years: which patients may benefit?
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ABSTRACT:
SUBMITTER: Haen SP
PROVIDER: S-EPMC5030379 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Allogeneic hematopoietic cell transplantation in patients ⩾70 years: which patients may benefit?
Haen S P SP Pham M M Faul C C Dörfel D D Vogel W W Kanz L L Bethge W A WA
Blood cancer journal 20160708 7
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Project description:In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥70 years with hematologic malignancies across the United States. Adults ≥70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥70 years underwent HCT across 103 transplant centers. The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% [95% confidence interval (CI), 21% to 33%] in 2000-2007 to 39% [95% CI, 35% to 42%] in 2008-2013, P < .001; PFS: 22% [16% to 28%] in 2000-2007 to 32% [95% CI, 29% to 36%] in 2008-2013, P = .003). Two-year TRM ranged from 33% to 35% and was unchanged over time (P = .54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ≥3 (hazard ratio [HR], 1.27; P = .006), umbilical cord blood graft (HR, 1.97; P = .0002), and myeloablative conditioning (HR, 1.61; P = .0002) as adverse factors. Over the past decade, utilization and survival after allogeneic transplant have increased in patients ≥70 years. Select adults ≥70 years with hematologic malignancies should be considered for transplant.
| S-EPMC5580273 | biostudies-literature
Project description:Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and have important roles in hematopoietic engraftment, GvHD and graft-versus-leukemia responses following allogeneic hematopoietic cell transplantation (HCT). In addition, pDCs mediate antiviral immunity, particularly as they are the body's primary cellular source of type I interferon. Given their pleiotropic roles, pDCs have emerged as cells that critically impact transplant outcomes, including overall survival. In this article, we will review the pre-clinical and clinical literature, supporting the crucial roles that pDCs assume as key immune effector cells during HCT.
| S-EPMC4862020 | biostudies-literature
Project description:IntroductionThe first series of patients with metastatic renal cell carcinoma (RCC) treated by non-myeloablative allogeneic hematopoietic cell transplantation (HCT) was reported in 2000 and demonstrated an allogeneic graft-versus-tumor (GVT) effect that encouraged further investigation of this approach. However, the past 10 years have also witnessed profound changes in the medical management of metastatic RCC with the introduction of targeted therapies directed against VEGF or mammalian target of rapamycin (mTOR) signaling pathways creating uncertainty about a continued role for allogeneic HCT in the treatment of RCC.Areas coveredA total of 21 published reports describing clinical outcomes for 398 patients with metastatic RCC treated by allogeneic HCT compiled herein provide a composite overview of the world wide experience for key efficacy and toxicity outcomes. Review of correlative studies that identify donor-derived T cells as mediators of RCC-specific GVT effects offers insight into both the potential as well as the technical barriers to the delivery of antigen-specific post-transplant cellular therapy or vaccination designed to augment the allogeneic GVT effect.Expert opinionThe future development of non-myeloablative allogeneic HCT for metastatic RCC will require novel treatment protocols designed to augment and sustain post-transplant GVT effects against RCC to generate renewed enthusiasm for this approach.
| S-EPMC3201801 | biostudies-literature
Project description:Hematologic malignances are more common and often higher risk in older patients. Allogeneic hematopoietic cell transplantation (alloHCT) best enables long-term disease control for patients with poor risk or relapsed/refractory hematologic malignancies such as acute myeloid leukemia, myelodysplastic syndromes, or myelofibrosis. Rates of alloHCT among older patients, while still relatively low compared with younger patients, have risen sharply over the past decade. Accumulating evidence supports alloHCT for patients ≥60 years of age relative to non-HCT therapies based on improved overall and disease-free survival. However, a significant proportion of older adults have limitations characterized by geriatric assessment. A systematic process to evaluate and optimize older patients may improve decision making, transplant outcomes, and alloHCT access. We present case-based studies to illustrate a stepwise and rational approach to proper older patient evaluation, pretransplant optimization, and posttransplant care with attention to important geriatric issues and quality of life.
| S-EPMC8791130 | biostudies-literature
Project description:BackgroundThis retrospective, historically controlled investigative study examined the benefit of a nutritional support pathway that included nutritional education before the start of conditioning and emphasized oral nutrition in response to nutrition-related adverse events in patients undergoing hematopoietic stem cell transplantation (HSCT).Material and methodsParticipants were patients undergoing allogeneic HSCT; 46 were in the control group (i.e., did not follow our nutritional pathway) and 36 were in the group that underwent nutritional intervention (enhanced nutrition group). We compared the following parameters between groups from the day before the start of conditioning to the day after completion of parenteral nutrition (PN): percent loss of body weight (%LBW), percent loss of skeletal muscle mass (%LSMM), and estimated basal energy expenditure (EBEE) sufficiency rate. The relationship between each parameter and %LBW was also examined. We also compared nutritional indices, gastrointestinal graft versus host disease (GvHD) grade, oral energy intake, and %LBW between groups.ResultsThere was a relationship between %LBW, %LSMM, and EBEE sufficiency rate in both groups. Compared with the control group, the enhanced nutrition group had significantly improved energy intake amount, EBEE sufficiency rate, PN duration, and oral energy intake over time. The enhanced nutrition group also had increased oral energy intake, no difference in gastrointestinal GvHD grade, and improved %LBW compared with the control group.ConclusionsUse of our nutritional support pathway in patients undergoing HSCT may be beneficial for %LBW and gastrointestinal GvHD grade, enabling early enhanced nutritional intervention after HSCT.
| S-EPMC6754707 | biostudies-literature
Project description: Not available
| S-EPMC10079542 | biostudies-literature
Project description:BackgroundA second allogeneic transplantation after a prior allogeneic (allo-allo) or autologous (auto-allo) hematopoietic cell transplantation (HCT) is usually performed for graft failure, disease recurrence, secondary malignancy, and, as planned, auto-allo transplantation for some diseases.MethodsWe sought to describe the costs of second allogeneic HCT and evaluate their relationship with patient characteristics and posttransplantation complications. Clinical information and medical costs for the first 100 days after transplantation of 245 patients (allo-allo, 55; auto-allo, 190) who underwent a second HCT between 2004 and 2010 were collected.ResultsMedian costs of the second allogeneic HCT were U.S. $151,000 (range, U.S. $62,000-405,000) for the allo-allo group and U.S. $109,000 (range, U.S. $26,000-490,000) for the auto-allo group. Median length of hospital stay was 23 days (range, 0-76) for the allo-allo group and 9 days (range, 0-96) for the auto-allo group. Only the year of transplantation and posttransplantation complications were significantly associated with costs in both groups when both pre- and posttransplantation variables were considered. The overall costs of the second HCT were higher than the first in the allo-allo group. For the auto-allo group, there was no difference between the costs whether preformed as a planned tandem or as salvage for relapse.ConclusionsOur results suggest that second allogeneic HCT is costly, particularly if it follows a prior allogeneic transplantation, and is driven by the costs of complications.
| S-EPMC3696423 | biostudies-literature
Project description:BackgroundOver the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation.MethodsWe analyzed overall mortality, mortality not preceded by relapse, recurrent malignant conditions, and the frequency and severity of major complications of transplantation, including graft-versus-host disease (GVHD) and hepatic, renal, pulmonary, and infectious complications, among 1418 patients who received their first allogeneic transplants at our center in Seattle in the period from 1993 through 1997 and among 1148 patients who received their first allogeneic transplants in the period from 2003 through 2007. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for the severity of illness at the time of transplantation.ResultsIn the 2003-2007 period, as compared with the 1993-1997 period, we observed significant decreases in mortality not preceded by relapse, both at day 200 (by 60%) and overall (by 52%), the rate of relapse or progression of a malignant condition (by 21%), and overall mortality (by 41%), after adjustment for components of the PAM score. The results were similar when the analyses were limited to patients who received myeloablative conditioning therapy. We also found significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs.ConclusionsWe found a substantial reduction in the hazard of death related to allogeneic hematopoietic-cell transplantation, as well as increased long-term survival, over the past decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD. (Funded by the National Institutes of Health.).
| S-EPMC3017343 | biostudies-literature
Project description:The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these discoveries and describe strategies being investigated to manipulate the microbiome for favorable outcomes, such as the proper selection and timing of antibiotics, type of diet and route of administration, probiotics, prebiotics, and fecal microbiota transplantation.
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Project description:Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68). Among the 95 patients, 78 were in first complete remission (CR1) and 17 were in second complete remission (CR2). Three-year overall survival (OS) of 67% (95% confidence interval [CI], 57 to 76), leukemia-free survival of 56% (95% CI, 46 to 66), relapse incidence of 29% (95% CI, 20 to 38), and nonrelapse mortality of 15% (95% CI, 9 to 23) were encouraging. OS was best in younger patients (<20 years), but no significant differences were observed between those 20 to 40 years of age and those who were 40 years or older. A matched-pair analysis showed similar outcomes comparing MPAL cases to 375 acute myelogenous leukemia or 359 acute lymphoblastic leukemia cases. MPAL patients had more acute and a trend for more chronic graft-versus-host disease. No difference was observed between patients who underwent transplantation in CR1 versus those who underwent transplantation in CR2. AlloHCT is a promising treatment option for pediatric and adult patients with MPAL with encouraging long-term survival.
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