Spontaneous Complete Remission in a Patient with Acute Myeloid Leukemia and Severe Sepsis.
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ABSTRACT:
SUBMITTER: Mozafari R
PROVIDER: S-EPMC5546120 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:Patients with acute myeloid leukemia (AML) without complete remission (CR) or in first relapse (Rel1) can have extended leukemia control and survival after allogeneic hematopoietic cell transplantation (HCT). For patients in Rel1 or primary induction failure (PIF), transplantation versus treatment to achieve a second CR (CR2) and subsequent HCT might yield similar outcomes, but available comparative data are scarce. METHODS:Survival was analyzed in 4682 HCT recipients according to disease status: PIF (N = 1440), Rel1 (failing ?1 reinduction; N = 1256), and CR2 (N = 1986). RESULTS:Patient, disease, and transplantation characteristics were similar, except that patients in CR2 more often had performance scores of 90% to 100%, de novo AML, and longer CR1 duration. Adverse cytogenetics were more common in patients who experienced PIF. The 5-year survival rate adjusted for performance score, cytogenetic risk, and donor type for CR2 was 39% (95% confidence interval [CI], 37%-41%) compared with 18% (95% CI, 16%-20%) for HCT in Rel1 and 21% (95% CI, 19%-23%) in PIF (P < .0001). CONCLUSIONS:Although survival is superior for patients who undergo HCT in CR2, transplantation for selected patients in Rel1 or PIF may still be valuable. These data can guide decision making about additional salvage therapy versus prompt HCT for patients not in CR, but they also highlight that AML is intrinsically more treatable in patients who have favorable-risk cytogenetics, those with longer CR1 duration, and younger patients with better performance status. Cancer 2017;123:2025-2034. © 2017 American Cancer Society.
| S-EPMC5445001 | biostudies-literature
Project description:Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18-60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12).
| S-EPMC4450623 | biostudies-literature
Project description:Machine learning (ML) is a useful tool for advancing our understanding of the patterns and significance of biomedical data. Given the growing trend on the application of ML techniques in precision medicine, here we present an ML technique which predicts the likelihood of complete remission (CR) in patients diagnosed with acute myeloid leukemia (AML). In this study, we explored the question of whether ML algorithms designed to analyze gene-expression patterns obtained through RNA sequencing (RNA-seq) can be used to accurately predict the likelihood of CR in pediatric AML patients who have received induction therapy. We employed tests of statistical significance to determine which genes were differentially expressed in the samples derived from patients who achieved CR after 2 courses of treatment and the samples taken from patients who did not benefit. We tuned classifier hyperparameters to optimize performance and used multiple methods to guide our feature selection as well as our assessment of algorithm performance. To identify the model which performed best within the context of this study, we plotted receiver operating characteristic (ROC) curves. Using the top 75 genes from the k-nearest neighbors algorithm (K-NN) model (K = 27) yielded the best area-under-the-curve (AUC) score that we obtained: 0.84. When we finally tested the previously unseen test data set, the top 50 genes yielded the best AUC = 0.81. Pathway enrichment analysis for these 50 genes showed that the guanosine diphosphate fucose (GDP-fucose) biosynthesis pathway is the most significant with an adjusted P value = .0092, which may suggest the vital role of N-glycosylation in AML.
| S-EPMC6423478 | biostudies-literature
Project description:Advances in acute myeloid leukemia (AML) genomics and targeted therapies include the recently approved BCL2 inhibitor venetoclax. The association between BCL2 expression and patient outcome was analyzed in a series of 176 consecutive AML patients at diagnosis (Dx), post-induction (PI), complete remission (CR) and relapse (RL). Levels increased significantly at relapse (mean 1.07 PI/0.96 CR vs. 2.17 RL, p = 0.05/p = 0.03). In multivariate analysis, high BCL2-Dx were marginally associated with worse progression-free survival, while high PI levels or at CR had an independent negative impact on outcome (PI: HR 1.58, p = 0.014; CR: HR 1.96, p = 0.008). This behavior of high PI or CR BCL2 levels and increased risk was maintained in a homogeneous patient subgroup of age <70 and intermediate cytogenetic risk (PI: HR 2.44, p = 0.037; CR: HR 2.71, p = 0.049). Finally, for this subgroup, high BCL2 at relapse indicated worse overall survival (OS, HR 1.15, p = 0.05). In conclusion, high BCL2 levels PI or at CR had an independent negative impact on patient outcome. Therefore, BCL2 expression is a dynamic marker that may be useful during AML patient follow up, and BCL2 levels at PI and/or CR may influence response to anti-BCL2 therapy.
| S-EPMC7762084 | biostudies-literature
Project description:Acute undifferentiated leukemia (AUL) is a subtype of acute leukemias of ambiguous lineage. There is no standard treatment approach for AUL, although acute lymphoblastic leukemia-like regimens for induction therapy have been used. Additional data suggest that AUL may be better treated as acute myeloid leukemia (AML), given their similarities in genetic, cytogenetic, and gene expression patterns. Somatic mutations of IDH1 are found in 7% to 14% of patients with AML; however, the patient in this study was the first patient with IDH1-mutated AUL treated with ivosidenib. In this case, a woman aged 39 years was found to have anemia and thrombocytopenia after presenting to her primary care physician with fatigue, weight loss, and persistent infections. During further workup of the cytopenia, she was diagnosed with AUL and received 7+3 (daunorubicin, 60 mg/m2/d intravenously on days 1-3, and cytarabine, 100 mg/m2 24-hour continuous intravenous infusion on days 1-7) due to the presence of the IDH1 mutation. Bone marrow biopsy performed on day 14 of 7+3 showed persistent disease, and ivosidenib was initiated due to severe HLA alloimmunization (panel-reactive antibody, 100%) and significant bleeding complications. The patient achieved a complete morphologic and molecular remission on ivosidenib monotherapy despite critical bleeding complications during induction. Targeted therapy using ivosidenib may represent an encouraging therapeutic option in patients with AUL and IDH1 mutations. Additional evaluation of ivosidenib in this subgroup of patients with AUL is needed.
| S-EPMC8162795 | biostudies-literature
Project description:Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) (n?=?8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR?=?1.33 [95%?CI?=?1.21-1.48]; p?<?10-5), LFS (HR?=?1.32 [95% CI?=?1.19-1.45]; p?<?10-5) and GRFS (HR?=?1.2 [95%?CI?=?1.1-1.31]; p?<?10-4) and higher NRM (HR?=?1.37 [95%?CI?=?1.17-1.59]; p?<?10-4) and RI (HR?=?1.27 [95% CI?=?1.12-1.44]; p?<?10-3). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1.
| S-EPMC7054545 | biostudies-literature
Project description:BackgroundAutophagy is a conserved recycling process in cells. However, the effects of autophagy on the remission and treatment response of acute myeloid leukemia (AML) patients have not been clarified.MethodsThe expression of MAP1LC3B, ATG5, ATG10, RB1CC1, and AMBRA1 genes was assessed in 32 newly diagnosed AML patients, 18 complete remission (CR) patients, and seven relapsed patients, as well as 15 controls, by real-time polymerase chain reaction (PCR).ResultsThe expression of all five genes was significantly higher in the newly diagnosed AML patients as compared to the controls (p < 0.0001). The MAP1LC3B, ATG5, ATG10, RB1CC1, and AMBRA1 gene expression significantly reduced in CR patients compared to newly diagnosed AML patients (p = 0.006, 0.003, 0.0002, 0.006, and 0.004, respectively). The AMBRA1 gene expression was significantly higher in the relapsed cases as compared to both newly diagnosed (p = 0.01) and CR patients (p = 0.03). Moreover, a significant positive correlation was observed between the expression of MAP1LC3B (r = 0.739, p = 0.000001), ATG5 (r = 0.682, p = 0.00001), and ATG10 (r = 0.586, p = 0.0004) genes and white blood cell (WBC) count in patients at diagnosis.ConclusionThe expression of MAP1LC3B, ATG5, ATG10, RB1CC1, and AMBRA1 genes can be examined to follow-up the remission of AML and the patient's response to treatment.
| S-EPMC8922948 | biostudies-literature
Project description:HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.
| S-EPMC6595262 | biostudies-literature
Project description:The treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) in reproductive-aged women poses major dilemmas concerning its associated teratogenicity as observed in many animal studies. Much controversy exists regarding continuation versus discontinuation of its use in pregnancy with some studies suggesting safety of TKIs before and during pregnancy and others reporting toxicity and adverse outcomes. TKIs have become a well-established treatment option for CML, significantly improving prognosis, and yet have been reported to be fetotoxic. We present a case of a 25-year-old woman who achieved successful pregnancy and delivery after withholding treatment, meanwhile relapsing, eventually achieving complete molecular remission after reinitiation of high dose dasatinib.
| S-EPMC5559931 | biostudies-other
Project description:Patients with acute myeloid leukemia (AML) frequently fail chemotherapy due to refractory disease, relapse, or toxicity. Among older AML patients (age > 60 years), there are few long-term survivors. Lenalidomide is a candidate for study in AML based on its clinical activity in a related disorder, myelodysplastic syndrome (MDS), with the 5q- chromosomal abnormality. We report induction of sustained morphologic and cytogenetic complete remission in 2 older AML patients treated with high-dose, single-agent lenalidomide; each patient had trisomy 13 as the sole cytogenetic abnormality. We show for the first time that lenalidomide has clinical activity in this poor-risk cytogenetic subset of AML. The clinical trials described in this paper have been registered with www.clinicaltrials.gov under identifiers NCT00466895 and NCT00546897.
| S-EPMC2947363 | biostudies-literature