13 results on '"Luft, Thomas"'
Search Results
2. The remission status of AML patients after allo-HCT is associated with a distinct single-cell bone marrow T-cell signature.
- Author
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Mathioudaki A, Wang X, Sedloev D, Huth R, Kamal A, Hundemer M, Liu Y, Vasileiou S, Lulla P, Müller-Tidow C, Dreger P, Luft T, Sauer T, Schmitt M, Zaugg JB, and Pabst C
- Subjects
- Humans, Bone Marrow pathology, CD8-Positive T-Lymphocytes pathology, Recurrence, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Abstract: Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells might lead to an insufficient graft-versus-leukemia (GVL) effect and relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) T lymphocytes and CD34+ cells of 6 patients with AML 100 days after allo-HCT to identify T-cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in CR vs REL samples. Pseudotime and gene regulatory network analyses revealed that CR CD8+ T cells were more advanced in maturation and had a stronger cytotoxicity signature, whereas REL samples were characterized by inflammatory tumor necrosis factor/NF-κB signaling and an immunosuppressive milieu. We identified ADGRG1/GPR56 as a surface marker enriched in CR CD8+ T cells and confirmed in a CD33-directed chimeric antigen receptor T cell/AML coculture model that GPR56 becomes upregulated on T cells upon antigen encounter and elimination of AML cells. We show that GPR56 continuously increases at the protein level on CD8+ T cells after allo-HCT and confirm faster interferon gamma (IFN-γ) secretion upon re-exposure to matched, but not unmatched, recipient AML cells in the GPR56+ vs GPR56- CD8+ T-cell fraction. Together, our data provide a single-cell reference map of BM-derived T cells after allo-HCT and propose GPR56 expression dynamics as a surrogate for antigen encounter after allo-HCT., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2024
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3. Pre-Transplant Serum Leptin Levels and Relapse of Acute Myeloid Leukemia after Allogeneic Transplantation.
- Author
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Schwarzbich MA, Dai H, Kordelas L, Beelen DW, Radujkovic A, Müller-Tidow C, Dreger P, and Luft T
- Subjects
- Humans, Leptin, Recurrence, Retrospective Studies, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute etiology
- Abstract
Weight loss and metabolic activity influence outcome after allogeneic stem cell transplantation (alloSCT). This study evaluates pre-conditioning Leptin, a peptide hormone involved in metabolism and immune homeostasis, as a prognostic factor for survival, relapse and non-relapse mortality (NRM) following alloSCT. Leptin serum levels prior to conditioning were determined in a cohort of patients transplanted for various hematologic malignancies ( n = 524) and correlated retrospectively with clinical outcome. Findings related to patients with acute leukemia (AL) from this sample were validated in an independent cohort. Low pre-conditioning serum Leptin was an independent prognostic marker for increased risk of relapse (but not of NRM and overall mortality) following alloSCT for AL of intermediate and advanced stage (beyond first complete remission). Multivariate analysis revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59-0.96, p = 0.020). This effect was similar in an independent validation cohort. Pre-conditioning serum Leptin was validated as a prognostic marker for early relapse by fitting the multivariate Cox model to the validation data. Pre-conditioning serum Leptin levels may serve as an independent prognostic marker for relapse following alloSCT in intermediate and advanced stage AL patients. Prospective studies are required to prove whether serum Leptin could be used for guiding nutritional intervention in patients with AL undergoing alloSCT.
- Published
- 2022
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4. Pre-transplant testosterone and outcome of men after allogeneic stem cell transplantation.
- Author
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Radujkovic A, Kordelas L, Krzykalla J, Benner A, Schult D, Majer-Lauterbach J, Beelen DW, Müller-Tidow C, Kasperk C, Dreger P, and Luft T
- Subjects
- Humans, Male, Prospective Studies, Retrospective Studies, Stem Cell Transplantation, Testosterone, Transplantation Conditioning, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute therapy
- Abstract
Testosterone is an important determinant of endothelial function and vascular health in men. As both factors play a role in mortality after allogeneic stem cell transplantation (alloSCT), we retrospectively evaluated the impact of pre-transplant testosterone levels on outcome in male patients undergoing alloSCT. In the discovery cohort (n=346), an impact on outcome was observed only in the subgroup of patients allografted for acute myeloid leukemia (AML) (n=176, hereafter termed 'training cohort'). In the training cohort, lower pre-transplant testosterone levels were significantly associated with shorter overall survival (OS) [hazard ratio (HR) for a decrease of 100 ng/dL: 1.11, P =0.045]. This was based on a higher hazard of non-relapse mortality (NRM) (cause-specific HR: 1.25, P =0.013), but not relapse (cause-specific HR: 1.06, P =0.277) in the multivariable models. These findings were replicated in a confirmation cohort of 168 male patients allografted for AML in a different center (OS, HR: 1.15, P =0.012 and NRM, cause-specific HR: 1.23; P =0.008). Next, an optimized cut-off point for pre-transplant testosterone was derived from the training set and evaluated in the confirmation cohort. In multivariable models, low pre-transplant testosterone status (<250 ng/dL) was associated with worse OS (hazard ratio 1.95, P =0.021) and increased NRM (cause-specific HR 2.68, P =0.011) but not with relapse (cause-specific HR: 1.28, P =0.551). Our findings may provide a rationale for prospective studies on testosterone/androgen assessment and supplementation in male patients undergoing alloSCT for AML., (Copyright© 2020 Ferrata Storti Foundation.)
- Published
- 2020
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5. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial.
- Author
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Beelen DW, Trenschel R, Stelljes M, Groth C, Masszi T, Reményi P, Wagner-Drouet EM, Hauptrock B, Dreger P, Luft T, Bethge W, Vogel W, Ciceri F, Peccatori J, Stölzel F, Schetelig J, Junghanß C, Grosse-Thie C, Michallet M, Labussiere-Wallet H, Schaefer-Eckart K, Dressler S, Grigoleit GU, Mielke S, Scheid C, Holtick U, Patriarca F, Medeot M, Rambaldi A, Micò MC, Niederwieser D, Franke GN, Hilgendorf I, Winkelmann NR, Russo D, Socié G, Peffault de Latour R, Holler E, Wolff D, Glass B, Casper J, Wulf G, Menzel H, Basara N, Bieniaszewska M, Stuhler G, Verbeek M, Grass S, Iori AP, Finke J, Benedetti F, Pichlmeier U, Hemmelmann C, Tribanek M, Klein A, Mylius HA, Baumgart J, Dzierzak-Mietla M, and Markiewicz M
- Subjects
- Adult, Aged, Disease-Free Survival, Female, Humans, Male, Middle Aged, Vidarabine therapeutic use, Antineoplastic Agents therapeutic use, Busulfan analogs & derivatives, Busulfan therapeutic use, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Transplantation Conditioning methods, Vidarabine analogs & derivatives
- Abstract
Background: Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population., Methods: We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18-70 years, had acute myeloid leukaemia in first or consecutive complete haematological remission (blast counts <5% in bone marrow) or myelodysplastic syndrome (blast counts <20% in bone marrow), Karnofsky index of 60% or higher, and were indicated for allogeneic HSCT but considered at an increased risk for standard myeloablative preparative regimens based on age (≥50 years), an HSCT-specific comorbidity index of more than 2, or both. Patients were randomly assigned (1:1) to receive either intravenous 10 g/m
2 treosulfan daily applied as a 2-h infusion for 3 days (days -4 to -2) or 0·8 mg/kg busulfan applied as a 2-h infusion at 6-h intervals on days -4 and -3. Both groups received 30 mg/m2 intravenous fludarabine daily for 5 days (days -6 to -2). The primary outcome was event-free survival 2 years after HSCT. The non-inferiority margin was a hazard ratio (HR) of 1·3. Efficacy was assessed in all patients who received treatment and completed transplantation, and safety in all patients who received treatment. The study is registered with EudraCT (2008-002356-18) and ClinicalTrials.gov (NCT00822393)., Findings: Between June 13, 2013, and May 3, 2016, 476 patients were enrolled (240 in the busulfan group received treatment and transplantation, and in the treosulfan group 221 received treatment and 220 transplanation). At the second preplanned interim analysis (Nov 9, 2016), the primary endpoint was met and trial was stopped. Here we present the final confirmatory analysis (data cutoff May 31, 2017). Median follow-up was 15·4 months (IQR 8·8-23·6) for patients treated with treosulfan and 17·4 months (6·3-23·4) for those treated with busulfan. 2-year event-free survival was 64·0% (95% CI 56·0-70·9) in the treosulfan group and 50·4% (42·8-57·5) in the busulfan group (HR 0·65 [95% CI 0·47-0·90]; p<0·0001 for non-inferiority, p=0·0051 for superiority). The most frequently reported grade 3 or higher adverse events were abnormal blood chemistry results (33 [15%] of 221 patients in the treosulfan group vs 35 [15%] of 240 patients in the busulfan group) and gastrointestinal disorders (24 [11%] patients vs 39 [16%] patients). Serious adverse events were reported for 18 (8%) patients in the treosulfan group and 17 (7%) patients in the busulfan group. Causes of deaths were generally transplantation-related., Interpretation: Treosulfan was non-inferior to busulfan when used in combination with fludarabine as a conditioning regimen for allogeneic HSCT for older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. The improved outcomes in patients treated with the treosulfan-fludarabine regimen suggest its potential to become a standard preparative regimen in this population., Funding: medac GmbH., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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6. EASIX for prediction of survival in lower-risk myelodysplastic syndromes.
- Author
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Merz A, Germing U, Kobbe G, Kaivers J, Jauch A, Radujkovic A, Hummel M, Benner A, Merz M, Dreger P, and Luft T
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Predictive Value of Tests, Proportional Hazards Models, Retrospective Studies, Risk Factors, Sex Factors, Survival Rate, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Models, Biological, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy
- Abstract
Patients with myelodysplastic syndromes (MDS) are at risk of early death from cardiovascular complications due to the link between clonal hematopoiesis and endothelial dysfunction. EASIX (Endothelial Activation and Stress Index) has been established to predict endothelial complications after allogeneic transplantation. We investigated the impact of EASIX measured at first diagnosis on survival of patients with lower- and higher-risk MDS (no allogeneic transplantation) in two independent institutions: n = 192 (training cohort) and n = 333 (validation cohort). Serum markers of endothelial cell distress were measured and correlated to EASIX. While no effects of EASIX on survival were observed in higher-risk patients, EASIX was associated with shorter survival in patients with lower-risk MDS in both cohorts (univariate: Cohort I: hazard ratio (HR): 1.46; 95% confidence interval (CI) 1.24-1.71; p-value < 0.001/Cohort II: HR 1.31 [1.17-1.48]; p-value < 0.001). Multivariate Cox regression analysis and prediction error analyses confirmed that EASIX remained a significant predictor of survival after adjustment for age, sex, cytogenetic abnormalities and bone marrow blasts in lower-risk patients. The model of the training cohort could be validated. Serum levels of Angiopioetin-2 correlated significantly with EASIX. We introduce EASIX as an easily accessible and independent predictor for survival in patients with lower-risk MDS.
- Published
- 2019
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7. Late treatment-related mortality versus competing causes of death after allogeneic transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia.
- Author
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Schetelig J, de Wreede LC, van Gelder M, Koster L, Finke J, Niederwieser D, Beelen D, Mufti GJ, Platzbecker U, Ganser A, Heidenreich S, Maertens J, Socié G, Brecht A, Stelljes M, Kobbe G, Volin L, Nagler A, Vitek A, Luft T, Ljungman P, Yakoub-Agha I, Robin M, and Kröger N
- Subjects
- Aged, Cause of Death, Disease-Free Survival, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Incidence, Male, Middle Aged, Recurrence, Retrospective Studies, Transplantation Conditioning mortality, Leukemia, Myeloid, Acute mortality, Myelodysplastic Syndromes mortality, Neoplasms, Second Primary mortality, Transplantation, Homologous mortality
- Abstract
The causes and rates of late patient-mortality following alloHCT for myelodysplastic syndromes or secondary acute myeloid leukemia were studied, to assess the contribution of relapse-related, treatment-related, and population factors. Data from EBMT on 6434 adults, who received a first alloHCT from January 2000 to December 2012, were retrospectively studied using combined land-marking, relative-survival methods and multi-state modeling techniques. Median age at alloHCT increased from 49 to 58 years, and the number of patients aged ≥65 years at alloHCT increased from 5 to 17%. Overall survival probability was 53% at 2 years and 35% at 10 years post-alloHCT. Survival probability at 5 years from the 2-year landmark was 88% for patients <45-year old and 63% for patients ≥65-year old at alloHCT. Cumulative incidence of nonrelapse mortality (NRM) for patients <45-year old at transplant was 7% rising to 25% for patients aged ≥65. For older patients, 31% of NRM-deaths could be attributed to population mortality. Favorable post-alloHCT long-term survival was seen; however, excess mortality-risk for all age groups was shown compared to the general population. A substantial part of total NRM for older patients was attributable to population mortality, information which aids the balanced explanation of post-HCT risk and helps improve long-term care.
- Published
- 2019
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8. Low serum vitamin D levels are associated with shorter survival after first-line azacitidine treatment in patients with myelodysplastic syndrome and secondary oligoblastic acute myeloid leukemia.
- Author
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Radujkovic A, Schnitzler P, Ho AD, Dreger P, and Luft T
- Subjects
- Adult, Aged, Aged, 80 and over, Calcitriol analogs & derivatives, Calcitriol pharmacology, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Leukemia, Myeloid, Acute blood, Male, Middle Aged, Myelodysplastic Syndromes blood, Retrospective Studies, Treatment Outcome, Vitamin D administration & dosage, Vitamin D antagonists & inhibitors, Azacitidine therapeutic use, Leukemia, Myeloid, Acute drug therapy, Myelodysplastic Syndromes drug therapy, Vitamin D blood
- Abstract
Background & Aims: Azacitidine (AZA) therapy has become the recommended first-line treatment for patients with high-risk myelodysplastic syndromes (MDS) and oligoblastic (<30% bone marrow blasts) acute myeloid leukemia (AML). However, improvement of the efficacy of AZA treatment remains a challenge. We retrospectively tested the hypothesis that VitD levels (25-hydroxyvitamin D3) prior to start of first-line AZA therapy are predictive of overall survival (OS) in patients diagnosed with MDS and secondary oligoblastic AML. Furthermore, the antiproliferative effects of AZA in combination with 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 were investigated in vitro., Methods: A total of 58 patients treated at our center between 2006 and 2014 were analyzed. Serum levels of VitD were quantified using a standard, commercially available 25-hydroxyvitamin D3 chemiluminescent immunoassay. Effects on cell proliferation were assessed using tetrazolium-based MTT assays., Results: Median serum VitD level prior to AZA treatment was 32.8 nM (range 11.0-101.5 nM). Patient, disease and treatment characteristics did not differ significantly between the low (≤32.8 nM; n = 29) and high (>32.8 nM; n = 29) VitD group. Estimated probability of 2-year OS in the low versus high VitD group was 14% versus 40% (P < 0.05). In multivariable analysis with OS as endpoint, adverse cytogenetics (HR 2.66, P = 0.03) and VitD (per 10 nM decrease, HR 1.68, P = 0.02) were independent predictors of worse survival. In-vitro treatment of myeloid cell lines with AZA in combination with VitD produced synergistic and additive antiproliferative effects. Addition of nanomolar VitD concentrations to AZA resulted in potentiation of AZA activity. Conversely, combination with the VitD antagonist TEI-9647 resulted in inhibition of AZA activity., Conclusions: Our study suggests that higher VitD levels were associated with a survival advantage following first-line AZA therapy. Enhanced cytotoxic effects upon combination treatment may contribute to the observed clinical effects. VitD repletion/supplementation during AZA treatment should be explored., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)
- Published
- 2017
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9. Expression of CDKN1C in the bone marrow of patients with myelodysplastic syndrome and secondary acute myeloid leukemia is associated with poor survival after conventional chemotherapy.
- Author
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Radujkovic A, Dietrich S, Andrulis M, Benner A, Longerich T, Pellagatti A, Nanda K, Giese T, Germing U, Baldus S, Boultwood J, Ho AD, Dreger P, and Luft T
- Subjects
- Adult, Aged, Aged, 80 and over, Antigens, CD34 metabolism, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Bone Marrow pathology, Bone Marrow Cells metabolism, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p57 genetics, Female, Gene Expression, Gene Expression Profiling, Hematopoietic Stem Cells metabolism, Humans, Immunohistochemistry, Leukemia, Myeloid, Acute drug therapy, Male, Middle Aged, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes pathology, Neoplasms, Second Primary drug therapy, Prognosis, Signal Transduction, Treatment Outcome, Young Adult, Bone Marrow metabolism, Cyclin-Dependent Kinase Inhibitor p57 metabolism, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute mortality, Myelodysplastic Syndromes metabolism, Myelodysplastic Syndromes mortality, Neoplasms, Second Primary metabolism, Neoplasms, Second Primary mortality
- Abstract
We tested the hypothesis that proliferative activity of hematopoietic stem cells has impact on survival in newly diagnosed patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). RNA expression profiles of CD34(+) cells were analyzed in 125 MDS patients and compared to healthy controls. Prognostic impact on overall survival (OS) of mRNA proliferation signatures established for solid tumor cells was analyzed retrospectively. For validation on the protein level, immunofluorescence and immunohistochemistry analyses in bone marrow (BM) biopsies were performed, and an independent cohort of 223 MDS and secondary AML patients was investigated. Lower proliferative activity correlated with the expression of cyclin-dependent kinase inhibitor 1C (CDKN1C) and with shorter OS (p < 0.001). In multivariable analysis, higher CDKN1C expression was associated with worse OS (p = 0.02). On the BM level, a total of 84 (38%) patients showed CDKN1C protein expression before start of treatment. Patient, disease and treatment characteristics did not differ between CDKN1C-positive and -negative patients. Positive CDKN1C BM status was associated with shorter OS in multivariable analysis (HR 1.54, p = 0.04). There was an interaction between CDKN1C BM status and subsequent treatment with negative impact on OS being most pronounced in patients receiving conventional cytotoxic chemotherapy (n = 83, 2-year OS 30% versus 58%, p = 0.002). In conclusion, low-proliferative phenotype and CDKN1C expression were associated with shorter OS. CDKN1C protein expression in the BM of newly diagnosed, treatment-naïve MDS and secondary AML patients was identified as a prognostic factor for poor survival in patients treated with antiproliferative chemotherapy., (© 2016 UICC.)
- Published
- 2016
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10. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia.
- Author
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Craddock C, Labopin M, Robin M, Finke J, Chevallier P, Yakoub-Agha I, Bourhis JH, Sengelov H, Blaise D, Luft T, Hallek M, Kröger N, Nagler A, and Mohty M
- Subjects
- Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic adverse effects, Azacitidine administration & dosage, Azacitidine adverse effects, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute mortality, Male, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes drug therapy, Prognosis, Recurrence, Salvage Therapy, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, Leukemia, Myeloid, Acute therapy
- Abstract
Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients received additional donor lymphocyte infusions. Forty-six of 157 (25%) assessable patients responded to azacitidine therapy: 24 (15%) achieved a complete remission and 22 a partial remission. Response rates were higher in patients transplanted in complete remission (P=0.04) and those transplanted for myelodysplastic syndromes (P=0.023). In patients who achieved a complete remission, the 2-year overall survival was 48% versus 12% for the whole population. Overall survival was determined by time to relapse post transplant more than six months (P=0.001) and percentage of blasts in the bone marrow at time of relapse (P=0.01). The concurrent administration of donor lymphocyte infusion did not improve either response rates or overall survival in patients treated with azacitidine. An azacitidine relapse prognostic score was developed which predicted 2-year overall survival ranging from 3%-37% (P=0.00001). We conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required., (Copyright© Ferrata Storti Foundation.)
- Published
- 2016
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11. Pretransplant metabolic distress predicts relapse of acute myeloid leukemia after allogeneic stem cell transplantation.
- Author
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Dietrich S, Radujkovic A, Stölzel F, Falk CS, Benner A, Schaich M, Bornhäuser M, Ehninger G, Krämer A, Hegenbart U, Ho AD, Dreger P, and Luft T
- Subjects
- Blood Proteins analysis, Body Mass Index, Humans, Leptin blood, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Recurrence, Retrospective Studies, Transplantation, Homologous, Weight Loss, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute etiology, Nutritional Status
- Abstract
Background: The impact of nutritional status on outcome of allogeneic stem cell transplantation (alloSCT) is controversial. This study investigates the influence of pretransplant weight loss and serologic indicators of nutritional homeostasis on relapse and death of acute myeloid leukemia (AML) after alloSCT., Methods: Pretransplant weight loss along with serum levels of total serum protein (TSP), albumin, C-reactive protein, and leptin were collected retrospectively in a training cohort (n = 149) and correlated with clinical outcome. Metabolic risk groups were defined and tested in an independent validation cohort (n = 167)., Results: We identified pretransplant weight loss and TSP as strong independent predictors of relapse and death. Patients in the metabolic high-risk group (low TSP and weight loss) had an increased risk for relapse (P = 0.0002) and death (P = 0.002), but a similar risk for acute graft-versus-host disease. Weight loss coincided with reduced pretransplant serum leptin levels. The adverse influence of weight loss and high metabolic risk on relapse and overall survival could be confirmed in the validation cohort and similarly in patients with less than or more than 5% blasts before alloSCT. Multivariate analysis of both cohorts revealed a hazard ratio for relapse of 7.78 (2.59-23.36, P = 0.0003) in the metabolic high risk group., Conclusion: Altered nutritional homeostasis before alloSCT correlates with recurrence of AML after transplantation. Studies addressing pretransplant nutritional interventions to reduce AML relapse rates are warranted.
- Published
- 2015
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12. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions--a retrospective multicenter analysis from the German Cooperative Transplant Study Group.
- Author
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Schroeder T, Rachlis E, Bug G, Stelljes M, Klein S, Steckel NK, Wolf D, Ringhoffer M, Czibere A, Nachtkamp K, Dienst A, Kondakci M, Stadler M, Platzbecker U, Uharek L, Luft T, Fenk R, Germing U, Bornhäuser M, Kröger N, Beelen DW, Haas R, and Kobbe G
- Subjects
- Adult, Aged, Allografts, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Recurrence, Retrospective Studies, Survival Rate, Antimetabolites, Antineoplastic administration & dosage, Azacitidine administration & dosage, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Lymphocyte Transfusion, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy
- Abstract
To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts <13% (HR, .54; 95% CI, .32 to .91; P = .021) were associated with better OS. Accordingly, 2-year OS rate was higher in MDS patients (66% ± 10%, P = .001) and correlated with disease burden in patients with AML. In summary, Aza and DLI is an effective and well-tolerated treatment option for patients with relapse after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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13. Azacitidine and low-dose cytarabine in palliative patients with acute myeloid leukemia and high bone marrow blast counts--a retrospective single-center experience.
- Author
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Radujkovic A, Dietrich S, Bochtler T, Krämer A, Schöning T, Ho AD, Dreger P, and Luft T
- Subjects
- Adult, Aged, Aged, 80 and over, Azacitidine adverse effects, Bone Marrow drug effects, Cytarabine adverse effects, Drug Administration Schedule, Female, Hemorrhage chemically induced, Humans, Karyotyping, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Neutropenia chemically induced, Palliative Care, Pneumonia chemically induced, Retrospective Studies, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols, Azacitidine administration & dosage, Bone Marrow pathology, Cytarabine administration & dosage, Leukemia, Myeloid, Acute drug therapy
- Abstract
We retrospectively analyzed and compared the efficacy and toxicity of azacitidine (AZA) and low-dose cytarabine (LD-Ara-C) in 65 palliative patients with acute myeloid leukemia (AML) showing high bone marrow blast counts (≥30%) before start of treatment. Twenty-seven and 38 patients received AZA and LD-Ara-C, respectively. The median patient age was 71 yr. Patient and disease characteristics did not differ between the treatment groups, except for BM blast counts, and peripheral leukocyte and blast counts which were significantly higher in the LD-Ara-C group. AZA and LD-Ara-C were first-line treatment in 12 (44%) and 17 patients (45%), respectively. Response and hematologic improvement rates were low and similar in both treatment groups. In both treatment groups, most common non-hematologic toxicities included febrile neutropenia, pneumonia, and bleedings without significant differences regarding frequencies. Estimated 1-yr survival rates were 15% (95% CI 8-22) and 13% (95% CI 7-19) in the AZA and LD-Ara-C groups, respectively, without statistically significant difference. In multivariate analysis (n = 65), previous treatment (HR 2.27, 95% CI 1.00-5.22, P = 0.05) and adverse cytogenetics (HR 2.50, 95% CI 1.20-5.22, P = 0.02) were independent predictors of poor survival. In our center and within the limitations of a retrospective study, both treatment regimens showed similar but limited efficacy in palliative patients with AML and high BM blast counts., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2014
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