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1.
Bone Marrow Transplant ; 59(2): 232-238, 2024 02.
Article in English | MEDLINE | ID: mdl-38007531

ABSTRACT

Allogeneic haematopoietic cell transplantation (alloHCT) has curative potential counterbalanced by its toxicity. Prognostic scores fail to include current era patients and alternative donors. We examined adult patients from the EBMT registry who underwent alloHCT between 2010 and 2019 for oncohaematological disease. Our primary objective was to develop a new prognostic score for overall mortality (OM), with a secondary objective of predicting non-relapse mortality (NRM) using the OM score. AI techniques were employed. The model for OM was trained, optimized, and validated using 70%, 15%, and 15% of the data set, respectively. The top models, "gradient boosting" for OM (AUC = 0.64) and "elasticnet" for NRM (AUC = 0.62), were selected. The analysis included 33,927 patients. In the final prognostic model, patients with the lowest score had a 2-year OM and NRM of 18 and 13%, respectively, while those with the highest score had a 2-year OM and NRM of 82 and 93%, respectively. The results were consistent in the subset of the haploidentical cohort (n = 4386). Our score effectively stratifies the risk of OM and NRM in the current era but do not significantly improve mortality prediction. Future prognostic scores can benefit from identifying biological or dynamic markers post alloHCT.


Subject(s)
Artificial Intelligence , Hematopoietic Stem Cell Transplantation , Humans , Adult , Transplantation, Homologous , Neoplasm Recurrence, Local , Hematopoietic Stem Cell Transplantation/methods , Prognosis , Chronic Disease , Retrospective Studies
2.
3.
Bone Marrow Transplant ; 55(3): 633-640, 2020 03.
Article in English | MEDLINE | ID: mdl-31695173

ABSTRACT

Information regarding the curative role of allogeneic stem cell transplantation (allo-HCT) in systemic anaplastic large cell lymphoma (sALCL) is scarce. We analyzed the results of allo-HCT in patients with relapsed/refractory sALCL with special emphasis on the role of brentuximab vedotin (BV) as a bridge to allo-HCT. Forty-four patients (24 females, median age 38 years) with sALCL were included. Twenty-three patients (52%) received BV before allo-HCT; BV-treated patients were more heavily pretreated (≥3 lines of therapy in 74% vs. 38%, p = 0.04). Twenty-three patients (52%) were in complete remission (CR) at allo-HCT. Three-year nonrelapse mortality and incidence of relapse (IR) after allo-HCT were 7% and 40%, respectively. With a median follow-up of 39 (12-69) months for survivors, 3-year progression-free survival (PFS) and overall survival were 53% and 74%, respectively. Univariate analysis showed that heavily pretreated patients and those not in CR had a higher IR and a lower PFS. The use of BV before transplant did not impact on any of the outcomes. Allo-HCT is a curative therapeutic strategy in a significant proportion of patients with relapsed/refractory sALCL; BV does not seem to modify transplant-related outcomes but might be able to render more patients candidates for this curative treatment.


Subject(s)
Hematopoietic Stem Cell Transplantation , Immunoconjugates , Lymphoma, Large-Cell, Anaplastic , Adult , Bone Marrow , Female , Humans , Immunoconjugates/therapeutic use , Lymphoma, Large-Cell, Anaplastic/therapy , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation Conditioning
8.
Bone Marrow Transplant ; 51(11): 1441-1448, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27295269

ABSTRACT

Allogeneic stem cell transplantation (SCT) remains the best curative option for patients with refractory AML or with high-risk myelodysplastic syndrome (MDS). For decades, age alone had been widely used as the primary criterion to assess eligibility for allogeneic SCT; however, prospective studies to evaluate allogeneic SCT in elderly patients are still limited. A total of 187 patients (median age of 64 years, range 60-77 years) with AML (87%) or MDS (13%) transplanted between 1999 and 2014 were included in this retrospective analysis. Relapse-free survival (RFS) and overall survival (OS) at 3 years were 32% (95% confidence interval (CI): 25-39%) and 35% (95%CI: 27-42%), respectively. Overall survival was 49% (95%CI: 35-64%) in AML patients who were transplanted in first complete remission (CR1), but even patients with active disease did benefit from transplantation, showing an OS at 3 years of 30% (95%CI: 20-40%). Multivariate analysis revealed disease- and patient-specific risk indices as independent prognostic factors for OS and non-relapse mortality (NRM). In conclusion, our monocenter results indicate that patients should not be generally withheld from allogeneic SCT because of age or disease status only. Specific risk models incorporating disease status and disease-specific risk factors at the time of transplantation as well as existing comorbidities are helpful tools to assess transplantation-associated risk factors of elderly patients.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Risk Assessment/methods , Age Factors , Aged , Female , Hematopoietic Stem Cell Transplantation/mortality , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Retrospective Studies , Survival Analysis , Transplantation, Homologous , Treatment Outcome
10.
Leukemia ; 30(6): 1230-6, 2016 06.
Article in English | MEDLINE | ID: mdl-26859081

ABSTRACT

We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects ⩾60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts ⩾5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P=0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P=0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P=0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes.


Subject(s)
Leukemia, Myeloid, Acute/drug therapy , Adult , Aminoglutethimide/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/therapeutic use , Danazol/therapeutic use , Disease-Free Survival , Granulocyte Colony-Stimulating Factor , Humans , Induction Chemotherapy , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Middle Aged , Mitoxantrone/therapeutic use , Stem Cell Transplantation , Survival Rate , Tamoxifen/therapeutic use , Transplantation, Autologous , Treatment Outcome , Young Adult
11.
Bone Marrow Transplant ; 51(5): 654-62, 2016 May.
Article in English | MEDLINE | ID: mdl-26855152

ABSTRACT

Allogeneic hematopoietic cell transplantation (HCT) offers the chance of cure for patients with non-transformed follicular lymphoma (FL), but is associated with the risk of non-relapse mortality (NRM). The aim of this study was to identify subgroups of FL patients who benefit from HCT. The European Society for Blood and Marrow Transplantation (EBMT) Minimum-Essential-A Data of 146 consecutive patients who received HCT for FL between 1998 and 2008 were extracted from the database of the German Registry 'DRST'. Diagnosis of FL was verified by contact with the reference pathologists. Estimated 1-, 2- and 5-year overall survivals (OS) were 67%, 60% and 53%, respectively. Day 100 NRM was 15%. Thirteen out of 33 patients (40%) with treatment-refractory disease (RD) at the time of transplantation survived long term. Univariate statistical analysis suggested limited chronic GvHD, donor age ⩽42 years and TBI-based conditioning in treatment refractory patients to correlate with favorable OS. Independent prognostic factors for OS were treatment-sensitive disease and limited chronic GvHD for the whole cohort, and additionally TBI-based conditioning for the treatment refractory subgroup. In contrast, patient age ⩾55 years had no impact on outcome. Thus, HCT for FL is associated with acceptable NRM, and offers a substantial chance of cure for patients with RD or advanced age. Donors ⩽42 years should be preferred if available.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Lymphoma, Follicular/therapy , Adolescent , Adult , Age Factors , Aged , Female , Germany , Graft vs Host Disease , Humans , Lymphoma, Follicular/mortality , Male , Middle Aged , Prognosis , Registries , Salvage Therapy/methods , Survival Rate , Tissue Donors , Transplantation Conditioning/methods , Treatment Outcome , Whole-Body Irradiation , Young Adult
12.
Leukemia ; 30(3): 555-61, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26522083

ABSTRACT

DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/therapeutic use , Induction Chemotherapy/methods , Leukemia, Myeloid, Acute/drug therapy , Aged , Cytarabine/therapeutic use , Cytogenetic Analysis , Daunorubicin/therapeutic use , Female , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Remission Induction , Survival Analysis
14.
Bone Marrow Transplant ; 51(3): 351-7, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26618548

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this retrospective study, 601 patients were included. Patients received allo-SCT in CR1, CR2, CR >2 or in advanced disease in 69%, 15%, 2% and 14% of cases, respectively. With an overall follow-up of 58 months, 523 patients received a TBI-based regimen, whereas 78 patients received a chemotherapy-based regimen including IV busulfan-cyclophosphamide (IV Bu-Cy) (n=46). Unlike patients aged ⩾35 years, patients aged <35 years who received a TBI-based regimen displayed an improved outcome compared with patients who received a chemotherapy-based regimen (5-year leukemia-free survival (LFS) of 50% for TBI versus 18% for chemo-only regimen or IV Bu-Cy regimens, P=10(-5) and 10(-4), respectively). In multivariate analysis, use of TBI was associated with an improved LFS (hazard ratio (HR)=0.55 (0.34-0.86), P=0.01) and overall survival (HR=0.54 (0.34-0.87), P=0.01) in patients aged <35 years. In conclusion, younger adult patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.


Subject(s)
Busulfan/administration & dosage , Cyclophosphamide/administration & dosage , Hematopoietic Stem Cell Transplantation , Registries , Transplantation Conditioning/methods , Whole-Body Irradiation , Adult , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Survival Rate
15.
Bone Marrow Transplant ; 50(12): 1503-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26367236

ABSTRACT

TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2-15%). Acute GvHD grade II-IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24-48) and 51% (90% confidence interval: 37-65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305).


Subject(s)
Myeloablative Agonists/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Stem Cell Transplantation , Transplantation Conditioning/methods , Adolescent , Adult , Allografts , Busulfan/administration & dosage , Busulfan/adverse effects , Busulfan/analogs & derivatives , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Graft vs Host Disease/prevention & control , Humans , Male , Middle Aged , Myeloablative Agonists/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Transplantation Conditioning/adverse effects
16.
Bone Marrow Transplant ; 50(4): 485-92, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25599163

ABSTRACT

Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Salvage Therapy , Adolescent , Adult , Aged , Allografts , Disease-Free Survival , Female , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Survival Rate , Time Factors
17.
Leukemia ; 29(5): 1060-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25434303

ABSTRACT

The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3-internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Adolescent , Adult , Alleles , Disease-Free Survival , Female , Gene Expression Regulation, Leukemic , Humans , Kaplan-Meier Estimate , Karyotyping , Male , Middle Aged , Recurrence , Remission Induction , Transplantation, Homologous , Treatment Outcome , Young Adult , fms-Like Tyrosine Kinase 3/genetics , fms-Like Tyrosine Kinase 3/metabolism
20.
Bone Marrow Transplant ; 48(8): 1070-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23376821

ABSTRACT

After allo-SCT, analysis of CD34(+) lineage-specific donor cell chimerism (DCC) is a sensitive method for monitoring minimal residual disease in patients with AML or myelodysplastic syndrome (MDS) with CD34 expression. To substantiate evidence of whether immune interventions in patients with impending relapse, defined by incomplete lineage-specific DCC, may prevent hematological relapse, we performed a retrospective nested case control study. Unsorted and lineage-specific DCC were measured in 134 patients. Forty-three patients had an incomplete CD34(+)-DCC with no other evidence of relapse. After immediate tapering of immunosuppressive treatment (30 patients) and/or infusion of donor lymphocytes (10 patients), 21 patients remained in remission (conversion to complete lineage-specific DCC) and 22 relapsed. Relapse-free survival at 3 years of the 91 patients with stable DCC and of the 43 patients with incomplete DCC was 74% (95% confidence interval (CI), 64-83%) and 40% (95% CI, 24-58%), respectively. OS rates were 79% (95% CI, 70-88%) and 52% (95% CI, 35-69%), respectively. These results, with 49% of patients with impending relapse successfully treated with immune intervention, highly suggest that analysis of CD34(+)-DCC is an important tool for monitoring and the management of AML and MDS patients after allo-SCT.


Subject(s)
Antigens, CD34/immunology , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/immunology , Leukemia, Myeloid, Acute/surgery , Myelodysplastic Syndromes/surgery , Adolescent , Adult , Aged , Case-Control Studies , Chimerism , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myeloid, Acute/immunology , Male , Middle Aged , Myelodysplastic Syndromes/immunology , Recurrence , Retrospective Studies , Transplantation Chimera , Transplantation, Homologous , Young Adult
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