Acute myeloid leukemia is the second most common leukemia among United States adults with a median age of 69 years. We investigated recent clinical practices related to treatments and disease ...outcomes in older patients with acute myeloid leukemia in the United States.
In this retrospective cohort study, we used Surveillance, Epidemiology, and End Results program data from 2000 through 2007 linked to Medicare enrollment and utilization data in the United States.
Among 5,480 patients with acute myeloid leukemia (median age 78 years, range 65-93), 38.6% received leukemia therapy within three months of diagnosis (treated group). Practice changed with 16.3% of treated patients receiving hypomethylating agents after 2004 when those agents became available. Median survival was two months in the untreated group versus six months in the treated group (P<0.01) with the biggest improvements seen in those aged 65-69 years (10 months vs. 4 months; P<0.01) and 70-74 years (8 months vs. 3 months; P<0.01). In 46 patients receiving allogeneic hematopoietic cell transplantation (0.8%), the median survival from diagnosis was 22 months.
Therapy for leukemia improves overall survival in older acute myeloid leukemia patients. Based on their comorbidities, most patients up to 80 years of age should be considered for treatment. New therapies including hypomethylating agents and allogeneic hematopoietic cell transplantation are promising and must be compared with other chemotherapy regimens.
Acute Myeloid Leukemia Döhner, Hartmut; Weisdorf, Daniel J; Bloomfield, Clara D
The New England journal of medicine,
2015-Sep-17, Letnik:
373, Številka:
12
Journal Article
Abstract Management of relapsed leukemia following allogeneic transplantation is challenging. Intensive chemotherapy, donor lymphocyte infusions (DLI), or second transplantation have some value, but ...most reported series describe only a limited number of patients surviving beyond 2 or 3 years following relapse. Additionally, understandable selection-bias of reports describing the outcomes of intensive management approaches for relapsed leukemia confound generalizability to a broader population. However numerous reports suggest that second allogeneic transplantation for relapsed leukemia following an initial transplant may produce extended disease control and survival for patients with favorable performance status, remission at the time of second transplant, and most importantly a long interval between initial transplant and relapse. Reduced intensity conditioning for second allografts may be preferable and little data exists to suggest that a new donor will improve disease control by inducing a stronger graft-versus-leukemia effect. Improved measures to prevent the first relapse, however, may protect more patients and produce a greater fraction enjoying extended leukemia-free survival.
Summary
The prognosis of relapsed acute myeloid leukaemia (AML) is poor and treatment is challenging. While the most potent treatment modality for patients who achieve a complete remission after ...relapse is still allogeneic haematopoietic cell transplantation (allo‐HCT), both transplant‐related mortality and relapse rates are high and many patients are not candidates for this approach. After a few decades of relative stasis in this field, a large number of novel approaches have become available to tackle this highly fatal disease. This is mostly due to our improved understanding of disease pathogenesis (including targetable mutations) and the anti‐leukaemia potential of the immune system. Several small‐molecule inhibitors and immunotherapeutic options are being explored in clinical trials and many more are in pre‐clinical phase. Future studies will focus on novel and mechanistically driven combinations, sequential treatments, and low‐toxicity maintenance strategies. While cure of relapsed/refractory AML without allo‐HCT is currently unlikely, treatments are becoming less toxic and remissions are lasting longer.
Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this ...review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need.
The microbial communities in the mouth and colon are anatomically connected via the saliva. However, the extent to which oral microbes reach and successfully colonize the distal gut has been debated. ...To resolve this long-standing controversy, we used exact amplicon sequence variants generated from concurrently collected saliva/stool microbiota in 66 healthy adults from two countries to show that, with one exception (
), the two niches are completely distinct. Thus, there is no evidence for colonization of oral bacteria in the distal gut. This defines the healthy state to which pathological states could be compared. Finding the same bacteria in the mouth and stool may warrant clinical investigation for an underlying pathology.
The success of allogeneic hematopoietic cell transplantation (HCT) is typically assessed as individual complications, including graft-versus-host disease (GVHD), relapse, or death, yet no one factor ...can completely characterize cure without ongoing morbidity. We examined a novel composite end point of GVHD-free/relapse-free survival (GRFS) in which events include grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the first post-HCT year. In 907 consecutive University of Minnesota allogeneic HCT recipients (2000-2012), 1-year GRFS was 31% (95% confidence interval CI 28-34). Regression analyses showed age, disease risk, and donor type significantly influencing GRFS. Adults age 21+ had 2-fold worse GRFS vs children; GRFS did not differ beyond age 21. Adjusted for conditioning intensity, stem cell source, disease risk, age, and transplant year, HLA-matched sibling donor marrow resulted in the best GRFS (51%, 95% CI 46-66), whereas HLA-matched sibling donor peripheral blood stem cells were significantly worse (25%, 95% CI 20-30, P = .01). GRFS after umbilical cord blood transplants and marrow from matched unrelated donors were similar (31%, 95% CI 27-35 and 32%, 95% CI 22-42, respectively). Because GRFS measures freedom from ongoing morbidity and represents ideal HCT recovery, GRFS has value as a novel end point for benchmarking new therapies.
•GRFS is a new composite end point useful for comparing HCT techniques and represents ideal post-HCT recovery.•In our cohort of 907 allogeneic HCT recipients, 1-year GRFS was 31%, with best outcomes in recipients of marrow from matched sibling donors.
Because the outcome of allogeneic hematopoietic cell transplantation (HCT) is predominantly influenced by disease type and status, it is essential to be able to stratify patients undergoing HCT by ...disease risk. The Disease Risk Index (DRI) was developed for this purpose. In this study, we analyzed 13 131 patients reported to the Center for International Blood and Marrow Transplant Research who underwent HCT between 2008 and 2010. The DRI stratified patients into 4 groups with 2-year overall survival (OS) ranging from 64% to 24% and was the strongest prognostic factor, regardless of age, conditioning intensity, graft source, or donor type. A randomly selected training subgroup of 9849 patients was used to refine the DRI, using a multivariable regression model for OS. This refined DRI had improved prediction ability for the remaining 3282 patients compared with the original DRI or other existing schemes. This validated and refined DRI can be used as a 4- or 3-group index, depending on the size of the cohort under study, for prognostication; to facilitate the interpretation of single-center, multicenter, or registry studies; to adjust center outcome data; and to stratify patients entering clinical trials that enroll patients across disease categories.
•The DRI successfully stratified patients in a very large allogeneic transplantation registry cohort.•The DRI was refined by using this cohort to build a more inclusive and conditioning intensity–independent index.
Oral activated charcoal (OAC), a potent adsorbent with no systemic absorption, has been used for centuries to treat poisoning. Recent studies have suggested its potential efficacy in protecting the ...colonic microbiota against detrimental effects of antibiotics. In a dose-finding safety and feasibility clinical trial, 12 healthy volunteers not receiving antibiotics drank 4 different preparations made of 2 possible OAC doses (12 or 25 grams) mixed in 2 possible solutions (water or apple juice), 3 days a week for 2 weeks. Pre- and post-OAC stool samples underwent 16S rRNA gene sequencing and exact amplicon sequence variants were used to characterize the colonic microbiota. The preferred preparation was 12 grams of OAC in apple juice, with excellent safety and tolerability. OAC did not influence the gut microbiota in our healthy volunteers. These findings provide the critical preliminary data for future trials of OAC in patients receiving antibiotics.
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