Publications by authors named "Arnold Ganser"
Early death and intracranial hemorrhage prediction in acute promyelocytic leukemia: validation of a risk score in a chemotherapy plus ATRA cohort from an international consortium.
Haematologica
October 2024
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Introduction: The combined use of the BCL-2 inhibitor venetoclax with azacitidine now is the standard of care for patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy with outcomes exceeding those achieved with hypomethylating agents alone. Venetoclax in combination with intensive chemotherapy is also increasingly used both as frontline as well as salvage therapy. However, resistance to and relapse after venetoclax-based therapies are of major concern and outcomes after treatment failure remain poor.
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- This study examines the effects of IDH1 and IDH2 mutations on adult AML patients who received allogeneic hematopoietic cell transplantation, finding that 15.91% had IDH1 mutations and 26.27% had IDH2 mutations.* -
- Patients with IDH1 and IDH2 mutations experienced lower rates of acute graft-versus-host disease (GVHD) compared to those without mutations, with significant improvements in overall survival (OS) linked to IDH1 mutations.* -
- IDH2 mutations were associated with a lower relapse rate and better leukemia-free survival (LFS) and OS, particularly in patients without NPM1 mutations, indicating these mutations may lead to better outcomes post
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- The combination of all-trans retinoic acid and anthracyclines has greatly improved acute promyelocytic leukemia (APL) treatment outcomes, particularly in areas without access to arsenic trioxide.
- Despite these advances, low- and middle-income countries (LMIC) still struggle with high mortality rates during treatment due to inadequate management of complications.
- A study involving 806 APL patients across several South American countries showed a reduction in induction mortality to 14.6% and an 81% overall survival rate over four years, demonstrating the benefits of international clinical collaboration.
Article Synopsis
Patients with acute myeloid leukemia (AML) who experience relapse following allogeneic hematopoietic cell transplantation (alloHCT) face unfavorable outcomes regardless of the chosen relapse treatment. Early detection of relapse at the molecular level by measurable residual disease (MRD) assessment enables timely intervention, which may prevent hematological recurrence of the disease. It remains unclear whether molecular MRD assessment can detect MRD before impending relapse and, if so, how long in advance.
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- Nocardiosis is a serious infection that can occur after hematopoietic cell transplantation (HCT), and this study aimed to identify its risk factors and the impact of certain preventive treatments.
- A review of 64 cases of nocardiosis and 128 matched controls showed that factors like tacrolimus use, low lymphocyte counts, male sex, recent corticosteroid use, and previous CMV infections increased the risk of developing this infection.
- Conversely, patients on trimethoprim-sulfamethoxazole prophylaxis had a significantly lower risk of nocardiosis; however, those who did develop it had poorer survival rates compared to controls.
Allogeneic haematopoietic cell transplantation (allo-HCT) remains an option for tyrosine kinase inhibitor-resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high-risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry-based study of 1686 CML patients undergoing first allo-HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo-HCT was 46 years (IQR 36-55).
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- The study assessed the impact of variability and stability on the effectiveness and side effects of CD19 CAR T-cell therapy in 12 patients with B-cell malignancies treated with Tisagenlecleucel.
- Researchers used advanced flow cytometry to evaluate CAR T-cell characteristics before and after treatment, finding that most activation markers remained stable and didn’t correlate with therapeutic response or toxicity.
- An immune signature linked to neurotoxicity was identified, suggesting that detailed profiling and ongoing monitoring of CAR T-cells could improve the safety and efficacy of this therapy, pending further validation.
Article Synopsis
- Allogeneic hematopoietic cell transplantation (allo-HCT) is the most effective treatment for acute myeloid leukemia (AML) with complex karyotype (CK), but CK is diverse and can impact prognosis differently.
- In a study involving 236 patients, those with a pure hyperdiploid karyotype (pHDK) had significantly better 2-year outcomes (50% leukemia-free survival and 57% overall survival) compared to those with other cytogenetic abnormalities (HDK+) which had lower survival rates (31% and 36% respectively).
- pHDK AML is likely a separate cytogenetic category from HDK+ and has better treatment outcomes post-allo-HCT, highlighting
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- Researchers evaluated the transplant conditioning intensity (TCI) score on a group of 4060 patients with acute myeloid leukemia who underwent allogeneic hematopoietic cell transplantation between 2018 and 2021.
- Patients were categorized into three TCI categories (low, intermediate, high) based on their scores, allowing assessment of the TCI's ability to predict outcomes like non-relapse mortality and relapse risk.
- Results showed that the TCI score effectively stratified patients by risk, demonstrating its relevance in predicting complications associated with transplant conditioning regimens.
Most patients with acute myeloid leukemia (AML) develop refractory/relapsed (R/R) disease even in the presence of novel and targeted therapies. Given the biological complexity of the disease and differences in frontline treatments, there are therapies approved for only subgroups of R/R AML, and enrollment in clinical trials should be first priority. Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative strategy for most patients.
View Article and Find Full Text PDFThe role of autologous-allogeneic tandem stem cell transplantation (alloTSCT) followed by maintenance as upfront treatment for multiple myeloma is controversial. Between 2008 and 2014 a total of 217 multiple myeloma patients with a median age of 51 years were included by 20 German centers within an open-label, parallel-group, multicenter clinical trial to compare alloTSCT to autologous tandem transplantation (autoTSCT) followed by 2 years of maintenance therapy with thalidomide (100 mg/day) in both arms with respect to relapse/progression-free survival (PFS) and other relevant outcomes. A total of 178 patients underwent a second transplant (132 allogeneic, 46 autologous).
View Article and Find Full Text PDFWe investigated ≥ grade 3 (CTC-AE) organ toxicities for commercial CD19 chimeric antigen receptor T cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell Lymphoma in the European Society for Blood and Marrow Transplantation (EBMT) CAR-T registry. The incidence of ≥ grade 3 organ toxicities during the first 100 days after CAR-T was low and the most frequent were: renal (3.0%), cardiac (2.
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- * The cumulative incidence of VOD/SOS was low, with 1.8% at day 21 and 2.4% at day 100, indicating that most patients developed classical VOD/SOS with several risk factors present.
- * Treatment with defibrotide led to resolution in 58% of patients, with better outcomes seen in those with moderate severity
Donor lymphocyte infusions (DLIs) can directly target leukemic cells through a graft-versus-leukemia effect and play a key role in the prevention and management of relapse after allogeneic hematopoietic cell transplantation (alloHCT). Predictors of response to DLIs are not well established. We evaluated measurable residual disease (MRD) before, 30 and 90 days after DLI treatment as biomarkers of response.
View Article and Find Full Text PDFTherapeutic donor lymphocyte infusions (tDLI) are used to reinforce the graft-versus-leukemia (GvL) effect in relapse after allogeneic stem cell transplantation (alloSCT). In contrast, the role of prophylactic DLI (proDLI) in preventing leukemia relapse has been less clearly established, although supported by retrospective, case-control, and registry analyses. We report a prospective, monocentric, ten year cohort of patients with high risk acute leukemias (AL) or myelodysplasia (MDS) in whom proDLI were applied beyond day +120 post alloSCT to compensate for lack of GvL.
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- * Results indicated that the combination treatment (FLAVIDA) had a significantly higher overall response rate (78% vs. 47%) compared to FLA-IDA alone, with similar rates of measurable residual disease in patients who responded.
- * After treatment, a high percentage of patients proceeded to further therapies like allogeneic stem cell transplants, and while recovery times for neutrophils and platelets were similar, FLA-IDA showed better salvage potential for refractory patients.