Impact of blood count recovery on outcomes of acute myeloid leukemia patients achieving morphologic leukemia-free state.
Ontology highlight
ABSTRACT:
SUBMITTER: Cheng WY
PROVIDER: S-EPMC6002522 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Impact of blood count recovery on outcomes of acute myeloid leukemia patients achieving morphologic leukemia-free state.
Cheng Wen-Yan WY Zhu Yong-Mei YM Liu Zhao Z Weng Xiang-Qin XQ Sui Jing-Ni JN Chen Yun-Shuo YS Wang Shi-Yang SY Shen Yang Y
Blood cancer journal 20180607 6
Similar Datasets
Project description: Not available
| S-EPMC8126559 | biostudies-literature
Project description:International Working Group (IWG) and European LeukemiaNet (ELN) response definitions are utilized to evaluate the efficacy of new agents for childhood acute myeloid leukemia (AML) for regulatory purposes. However, these criteria are not consistent with definitions used in pediatric AML trials or with standard pediatric practice to proceed with subsequent therapy cycles prior to IWG/ELN-defined count recovery. We retrospectively analyzed data from the two most recent Phase 3 pediatric AML clinical trials conducted by the Children's Oncology Group (COG) to assess the incidence, timing, and prognostic significance of count recovery following induction chemotherapy. Of the patients with fewer than 5% bone marrow blasts at the end of first induction, 21.5% of patients proceeded to a second induction cycle prior to achieving ANC ≥ 500 cells/μL and platelets ≥ 50,000 cells/μL, both well below the IWG/ELN thresholds of ANC > 1000 cells/μL and platelets > 100,000 cells/μL. In these two sequential childhood AML Phase 3 trials, neither ANC nor platelet recovery predicted survival. Intensification of treatment through the initiation of subsequent therapy cycles prior to attainment of IWG/ELN-defined CR is common practice in clinical trials for children with AML, suggesting that updated response definitions are needed for pediatric AML.
| S-EPMC8833679 | biostudies-literature
Project description:Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01%) in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable DMR as a prelude to successful treatment-free remission (TFR), which occurs in approximately half of all CML patients who cease TKI therapy. The lack of overt relapse in such patients has been attributed to immunological control of CML. In this review, we discuss an immunological timeline to successful TFR, focusing on the immunology of CML during TKI treatment; an initial period of immune suppression, limiting antitumor immune effector responses in newly diagnosed CML patients, linked to an expansion of immature myeloid-derived suppressor cells and regulatory T cells and aberrant expression of immune checkpoint signaling pathways, including programmed death-1/programmed death ligand-1. Commencement of TKI treatment is associated with immune system re-activation and restoration of effector-mediated [natural killer (NK) cell and T cell] immune surveillance in CML patients, albeit with differing frequencies in concert with differing levels of molecular response achieved on TKI. DMR is associated with maximal restoration of immune recovery in CML patients on TKI. Current data suggest a net balance between both the effector and suppressor arms of the immune system, at a minimum involving mature, cytotoxic CD56dim NK cells may be important in mediating TFR success. However, a major goal remains in CML to identify the most effective pathways to target to maximize an advantageous immune response and promote TFR success.
| S-EPMC5402174 | 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:BackgroundIn a phase III trial, older patients with acute myeloid leukemia (N=485) received decitabine or treatment choice (supportive care or cytarabine). This post hoc analysis examined whether baseline renal and hepatic function and white blood cell (WBC) counts predicted response.MethodsBaseline WBCs and renal and liver function markers were tabulated for responders/nonresponders.ResultsNonresponders had higher mean baseline creatinine (P=0.005). Creatinine data showed no significant between-group differences by treatment within responder category.ConclusionsNo relationship was found between baseline WBCs or hepatic function and response. Higher baseline creatinine in nonresponders may not be clinically relevant.
| S-EPMC3939385 | biostudies-literature
Project description:ObjectivesSRSF2 mutations are known to be associated with poor outcomes in myelodysplastic neoplasm, but studies on their prognostic impact on acute myeloid leukemia (AML) remain limited. In this retrospective study, we analyzed clinical and pathologic characteristics of patients with AML and correlated the outcomes with SRSF2 mutations.MethodsWe characterized the morphologic, immunophenotypic, molecular, and clinical findings in AML with mutated SRSF2 and compared them with SRSF2 wild-type (WT) myeloid neoplasms (MNs).ResultsUsing next-generation sequencing, we identified 134 patients with MNs and SRSF2 mutations (85 with AML and 49 with MNs) in addition to 342 SRSF2-WT AMLs. Fifty-two (62%) patients with altered SRSF2 demonstrated a variable degree of morphologic dysplasia. The most frequent immunophenotypic aberrancies in SRSF2-mutant AML included diminished CD33 expression and overexpression of CD7, CD56, or CD123, similar to WT AML. More IDH1/2 (P = .015) and NPM1 (P = .002) mutations were seen in SRSF2-mutant AML than in SRSF2-mutant non-AML. Further, more IDH1/2, ASXL1, RUNX1, and STAG2 mutations were observed in SRSF2-mutant AML than in SRSF2-WT AML (P < .0001 to P = .001). Finally, patients with SRSF2-mutant AML showed a significantly worse overall survival (OS) than patients with SRSF2-WT AML (P < .0001), but this worse OS appeared to be rescued by allogeneic stem cell transplant (allo-SCT).ConclusionsAcute myeloid leukemia with altered SRSF2 shows a variable degree of morphologic dysplasia without uniform immunophenotypic aberrancies. SRSF2 mutations appear to be independent poor prognostic factors, but allo-SCT has improved the clinical outcomes in patients with SRSF2-mutant AML.
| S-EPMC10629464 | biostudies-literature
Project description: Not available
| S-EPMC10660393 | biostudies-literature
Project description:Chronic myeloid leukemia (CML) is initiated and maintained by BCR::ABL which is clinically targeted using tyrosine kinase inhibitors (TKIs). TKIs can induce long-term remission but are also not curative. Thus, CML is an ideal system to test our hypothesis that transcriptome-based state-transition models accurately predict cancer evolution and treatment response. We collected time-sequential blood samples from tetracycline-off (Tet-Off) BCR::ABL-inducible transgenic mice and wild-type controls. From the transcriptome, we constructed a CML state-space and a three-well leukemogenic potential landscape. The potential's stable critical points defined observable disease states. Early states were characterized by anti-CML genes opposing leukemia; late states were characterized by pro-CML genes. Genes with expression patterns shaped similarly to the potential landscape were identified as drivers of disease transition. Re-introduction of tetracycline to silence the BCR::ABL gene returned diseased mice transcriptomes to a near healthy state, without reaching it, suggesting parts of the transition are irreversible. TKI only reverted the transcriptome to an intermediate disease state, without approaching a state of health; disease relapse occurred soon after treatment. Using only the earliest time-point as initial conditions, our state-transition models accurately predicted both disease progression and treatment response, supporting this as a potentially valuable approach to time clinical intervention, before phenotypic changes become detectable.
| S-EPMC10997512 | biostudies-literature
Project description:Chronic myeloid leukemia (CML) is initiated and maintained by BCR::ABL which is clinically targeted using tyrosine kinase inhibitors (TKIs). TKIs can induce long-term remission but are also not curative. Thus, CML is an ideal system to test our hypothesis that transcriptome-based state-transition models accurately predict cancer evolution and treatment response. We collected time-sequential blood samples from tetracycline-off (Tet-Off) BCR::ABL-inducible transgenic mice and wild-type controls. From the transcriptome, we constructed a CML state-space and a three-well leukemogenic potential landscape. The potential's stable critical points defined observable disease states. Early states were characterized by anti-CML genes opposing leukemia; late states were characterized by pro-CML genes. Genes with expression patterns shaped similarly to the potential landscape were identified as drivers of disease transition. Re-introduction of tetracycline to silence the BCR::ABL gene returned diseased mice transcriptomes to a near healthy state, without reaching it, suggesting parts of the transition are irreversible. TKI only reverted the transcriptome to an intermediate disease state, without approaching a state of health; disease relapse occurred soon after treatment. Using only the earliest time-point as initial conditions, our state-transition models accurately predicted both disease progression and treatment response, supporting this as a potentially valuable approach to time clinical intervention even before phenotypic changes become detectable.
| S-EPMC10592732 | biostudies-literature
Project description:Reduced-intensity conditioning (RIC) umbilical cord blood (UCB) transplantation is increasingly used in hematopoietic stem cell transplantation (HCT) for older and medically unfit patients. Data on the efficacy of HCT after RIC relative to myeloablative conditioning (MAC) are limited. We compared the outcomes of acute myeloid leukemia (AML) patients >18 yrs who received UCB grafts after either RIC or MAC. One hundred nineteen adult patients with AML in complete remission (CR) underwent an UCB transplant after RIC (n =74, 62%) or MAC (n = 45, 38%) between January 2001 and December 2009. Conditioning was either reduced intensity and consisted of cyclophosphamide 50 mg/kg, fludarabine 200 mg/m(2), and total-body irradiation (TBI) 200 cGy or myelablative and consisted for cyclophosphamide 120 mg/kg, fludarabine 75 mg/m(2), and TBI 1200-1320 cGy. All patients received cyclosporine (day -3 to day +180) and mycophenolate mofetil (day -3 to day +45) post-HCT immunosuppression and hematopoietic growth factor. Use of RIC was reserved for patients >45 years (n = 66, 89%) or preexisting severe comorbidities (n = 8, 11%). The 2 groups were similar except for preceding myelodysplastic syndrome (RIC = 28% versus MAC = 4%, P < .01) and age that was dictated by the treatment protocols (median, RIC = 55 years versus MAC = 33years; P < .01). The incidence of neutrophil recovery at day +42 was higher with RIC (94% versus MAC = 82%, P < .1), whereas platelet recovery at the sixth month was similar (RIC = 68% versus MAC = 67%, P = .30). Incidence of grade II-IV acute graft-versus-host disease (aGVHD) (RIC = 47% versus MAC = 67%, P < .01) was decreased with similar incidence of chronic GVHD (cGVHD) (RIC = 30% versus MAC = 34%, P = .43). Median follow-up for survivors was 3.8 and 4.5 years for RIC and MAC, respectively (P = .4). Using RIC, 3-year leukemia-free survival (LFS) was decreased (31% versus MAC = 55%, P = .02) and 3-year relapse incidence was increased (43% versus MAC = 9%, P < .01). Two-year transplant-related mortality (TRM) was similar (RIC = 19% versus MAC = 27%; P = .55). In multivariate analysis, RIC recipients and those in CR2 with CR1 duration <1 year had higher risk of relapse and poorer LFS with no independent predictors of TRM. UCB with RIC extends the use of allogeneic HCT for older and frail patients without excessive TRM with greater benefit for patients in CR1 and CR2 with longer CR1.
| S-EPMC4130206 | biostudies-literature