Sie können Operatoren mit Ihrer Suchanfrage kombinieren, um diese noch präziser einzugrenzen. Klicken Sie auf den Suchoperator, um eine Erklärung seiner Funktionsweise anzuzeigen.
Findet Dokumente, in denen beide Begriffe in beliebiger Reihenfolge innerhalb von maximal n Worten zueinander stehen. Empfehlung: Wählen Sie zwischen 15 und 30 als maximale Wortanzahl (z.B. NEAR(hybrid, antrieb, 20)).
Findet Dokumente, in denen der Begriff in Wortvarianten vorkommt, wobei diese VOR, HINTER oder VOR und HINTER dem Suchbegriff anschließen können (z.B., leichtbau*, *leichtbau, *leichtbau*).
Fanconi anemia (FA) is a rare inherited disorder characterized by genomic instability, bone marrow failure, and a markedly increased risk of developing acute myeloid leukemia (AML). The intrinsic hypersensitivity of FA cells to DNA-damaging agents renders conventional chemotherapy particularly toxic and often ineffective.
Case Presentation
A 31-year-old woman with FA who progressed to AML and failed to achieve remission with standard induction therapy. Bone marrow blasts were initially 10%.
Intervention
As part of a clinical trial, she received CD56+ cell-based immunotherapy after FLAG chemotherapy. She subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched sibling donor using a CD3+/CD19-depleted graft. Post-transplant, she received additional infusions of CD56+ cells.
Outcome
CD56+ immunotherapy reduced bone marrow blasts from 10 to 3%, enabling successful HSCT. Post-transplant, she remained in complete remission with no detectable minimal residual disease (MRD) at both day +30 and day +90.
Conclusion
CD56+ cell-based immunotherapy can effectively decrease the leukemic burden in FA patients with AML, facilitating successful HSCT. This innovative approach may enhance outcomes for high-risk patients and merits further research.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Introduction
Fanconi anemia (FA) is a rare, cancer-predisposing, autosomal recessive bone marrow failure syndrome (Eghbali et al. 2024). Most patients with FA develop severe hematologic abnormalities, mainly myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML), with the highest frequency of leukemia occurring in the teenage years and early adulthood (Latour and Soulier 2016). To date, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative modality for FA patients with bone marrow failure (BMF) or advanced AML /MDS (Latour et al. 2013). However, due to the high sensitivity of FA patients to chemotherapy, achieving a stable condition poses a significant clinical challenge (Mehta et al. 2019) underscoring the unmet need for novel bridging strategies to facilitate safe transplantation.
Heterogeneous humoral and cellular immune dysfunction has been demonstrated in FA patients (Hashemi et al. 2021). In a study evaluating 29 FA patients, Myers et al. observed a decrease in natural killer (NK) cell count and cytotoxic activity compared to healthy controls (Myers et al. 2017). An imbalance between the CD56bright and CD56dim subsets of NK cells, marked by an increase in CD56bright NK cells and a reduction of CD16 expression on CD56dim NK cells, has also been reported in patients with FA (Justo et al. 2014). These findings suggest a rational basis for investigating NK cell-based therapeutic strategies in FA patients, especially for those who have developed acute leukemia.
Anzeige
Activated haploidentical NK cell therapy in patients with relapsed/refractory AML is well tolerated and leads to complete remission in 30–50% of cases, serving as an effective bridge to allogeneic HSCT (Cooley et al. 2017). In the context of transplantation, Lee and colleagues demonstrated that the administration of allogeneic NK cells following haplo-HCT in patients with high-risk AML and MDS protects patients against leukemia relapse without increasing the risk of graft-versus-host disease (GVHD) (Lee et al. 2023).
Herein, we present the clinical course of a patient with FA who progressed to AML and required HSCT. We highlight the therapeutic strategies employed to optimize the patient's pre-transplant condition, focusing on the potential application of CD56+ cell-based immunotherapy to enhance disease control and bridge to transplantation.
Case presentation
Patient
A 31-year-old woman with a known history of FA diagnosed at the age of 13 and confirmed by a positive blood chromosomal breakage test, was referred to the Bone Marrow Transplantation Unit of Taleghani Hospital for allogeneic HSCT. In December 2022, a bone marrow (BM) evaluation revealed hypocellularity with myeloid lineage dysplasia and 3% blasts. By April 2023, the patient exhibited disease progression, with 22% blasts detected in the BM aspiration, leading to a diagnosis of transformed AML. The karyotype formula was 46, XX, der(6) t(6;7) (p23; q32), der(7) t(7;21) (q22;q22), der(21) t(7;21) t (6;7) and molecular studies were negative for NPM1 and FLT3-ITD gene mutations.
Given the patient’s clinical condition, blast percentage, concurrent infection at the time of hospitalization, and treatment-related hepatic dysfunction, induction therapy was initiated using a reduced-intensity 5 + 2 regimen to minimize toxicity. After completing the induction cycle, BM reevaluation demonstrated persistent disease, with 10% blasts positive for CD34, CD117, CD33, CD64, and HLA-DR. Following this, high-dose cytarabine (HiDAC− 3 g/m2 infused i.v. over three nonconsecutive days, yielding a total cumulative dose of 12 g/m2) was administered as a consolidation regimen. In July 2023, flow cytometry of the BM revealed 7% myeloid blast cells, with strong expression of HLA-DR, CD34, CD117, CD14, and CD64; dim expression of CD45, and negativity for CD56. Given the patient's failure to achieve complete remission after conventional chemotherapy, she was subsequently enrolled in a clinical trial exploring CD56+ cell-based immunotherapy (IRCT20230801058996N2). Written informed consent was obtained before enrollment.
Anzeige
CD56+ enrichment
After signing the consent form, donors were chosen from healthy, HLA-haploidentical, first or second-degree relatives. HLA typing and KIR genotyping were performed, and the donor with the highest KIR–ligand mismatch was selected. The patient’s HLA typing was C2/C2 and Bw4/Bw6. For CD56+ cell infusion, we selected a donor who was KIR2DL2 positive, thereby creating a KIR–ligand mismatch between donor CD56+ cells and the patient’s HLA background.
Unstimulated peripheral blood mononuclear cells (PBMCs) were collected from the donor using the Cobe Spectra Apheresis System (Terumo BCT, USA) and then shipped to the central processing facility. CD56+ cells were magnetically enriched from PBMCs in a single-step enrichment protocol using the CliniMACS Plus system (Miltenyi Biotech, Germany) and CD56 MicroBeads. A sample of the final product was analyzed by flow cytometry to quantify T cells, B cells, NK cells, NKT cells, and monocytes following CliniMACS CD56-positive selection.
CD56+ activation
For activation, enriched CD56+ cells were incubated overnight in NKMACS® GMP medium (Miltenyi Biotech, Germany) supplemented with 5% fetal bovine serum (FBS) (HyClone™, United States), 1% NK MACS supplement, and 20 ng/mL of MACS® GMP-grade human IL-15 (Miltenyi Biotech, Germany). Following incubation, cells were washed with PBS/EDTA (Miltenyi Biotech, Germany) and prepared for infusion or cryopreservation.
Quality control of the final activated CD56+ cell product was performed to ensure safety, purity, and functionality before infusion. Before and after incubation with IL-15, the phenotype of CD56+ cells was evaluated by flow cytometry (MACS QUNT 10, Miltenyi Biotech, Germany). The cytotoxicity of activated CD56+ cells was assessed against the leukemia K562 cell line using the calcein-AM assay. Briefly, K562 cells (1 × 106) were harvested and centrifuged at 140 g for 7 min. Then cells were washed twice with FBS-free RPMI medium and resuspended in 1000 µL of the same medium. Calcein labeling was performed by adding 2 µL of working calcein solution, followed by incubation for 30 min at room temperature in the dark. The staining reaction was stopped by adding RPMI containing FBS for 5 min. Cells were then centrifuged again and resuspended in 500 µL of FBS-free RPMI. Cell count and viability were determined using trypan blue exclusion and a hemocytometer. For cytotoxicity assessment, CD56⁺ cells were used as effector cells and co-cultured with calcein-labeled K562 target cells at effector-to-target (E:T) ratios of 1:1, 5:1, and 10:1 in U-bottom 96-well plates, with a final volume of 200 µL FBS-free RPMI per well. Co-cultures were incubated for 4 h at 37 °C in a humidified atmosphere containing 5% CO₂. Calcein-labeled K562 cells cultured alone served as controls for spontaneous target cell death. After incubation, cells were washed, resuspended in PBS, and analyzed by flow cytometry.
CD56⁺ cell-mediated cytotoxicity was calculated as follows:
The flow cytometric gating strategy included: (i) identification of K562 cells based on SSC-A and calcein fluorescence (FITC channel), (ii) exclusion of doublets using FSC-A/FSC-H, and (iii) determination of target cell death based on PI positivity.
CD56+ therapy procedure
The patient received CD56⁺ cell infusions after the low-intensity FLAG chemotherapy regimen to reduce the remaining blasts. The FLAG regimen consisted of intravenous fludarabine (25 mg/m2/day), high-dose cytarabine (3 g/m2/day), and subcutaneous granulocyte colony-stimulating factor (G-CSF) at 5 μg/kg/day. Fludarabine and cytarabine were administered from day − 7 to day − 3, while G-CSF was given from day − 6 to day − 2 (Fig. 1). Two days after the final chemotherapy dose, on day 0, the patient received alloreactive CD56⁺ cells (1 × 10⁶ cells/kg), followed by a second infusion on day + 5 (3 × 10⁶ cells/kg) and a third infusion on day + 10 (5 × 10⁶ cells/kg) (Fig. 1). The first infusion consisted of freshly purified CD56⁺ cells, whereas the subsequent infusions were administered using cryopreserved aliquots that were thawed and washed before infusion. Before each infusion, the patient received intravenous premedication with chlorphenamine (10 mg/mL) and hydrocortisone (10 mg/mL) to mitigate potential infusion-related reactions. CD56⁺ cells were administered over approximately 40 min under close clinical monitoring.
Therapeutic efficacy was assessed 28 days following CD56⁺ cell administration using the European Leukemia Net (ELN) response criteria (Döhner et al. 2022). Safety was evaluated and documented according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 6.0.
Anzeige
Result
Following the separation process, the enriched CD56⁺ cell fraction contained 45.7% CD56+/CD3– NK cells and 52.1% CD56+/CD3+ NKT cells. The total cell yield was 2.13 × 109 cells, with a mean recovery rate of 75% and a 2.8 log reduction in CD3⁺ T cells. Microbiological assessments confirmed that the products were free of mycoplasma contamination and tested negative for bacterial endotoxins by the Limulus Amebocyte Lysate (LAL) assay and for microbial contamination using the BACTEC culture system. The expression levels of activation markers CD25 and CD69 on the CD56+ fraction were assessed, and a marked upregulation compared to the pre-selection baseline was observed, indicating successful activation of CD56+ cells (Fig. 1). Functional assessment revealed enhanced cytotoxicity against the K562 target cell line in a dose-dependent manner at E:T ratios of 1:1, 5:1, and 10:1 (Fig. 2).
Fig. 2
Phenotypic characterization, activation status, and quality control of IL-15 activated CD56⁺ cells. A Flow-cytometry plots showing CD56⁺ NK/NKT cell percentage before and after isolation. B Expression of activation markers and NK-cell receptors on CD56⁺ cells before (unactivated) and after IL-15 activation, including CD69, CD25, NKG2A, NKG2D, NKp30, and NKp46. C Calcein-AM–based cytotoxicity assay demonstrating the functional killing capacity of CD56⁺ cells
The patient received all three planned escalating doses of CD56⁺ cells on a weekly schedule following FLAG chemotherapy. The infusions were well tolerated, with no acute or delayed infusion-related toxicities observed. On day 28, response to therapy was evaluated via bone marrow aspiration by flow cytometry, which revealed a reduction in blasts to 3%. Given the complete morphological response and the underlying diagnosis of high-risk AML, the patient was subsequently referred for allogeneic HSCT. A fully matched (10/10) related-sibling donor was identified, and ex vivo CD3+ cell depletion was performed on donor grafts using the CliniMACS Plus system to mitigate the risk of GVHD. We also used an additional B-cell depletion with anti-CD19 microbeads to reduce the risk of EBV reactivation. On November 18th, 2023, the patient received a stem cell dose of 6.5 × 10⁶ CD34⁺ cells/kg. The conditioning regimen for haploidentical HSCT consisted of intravenous fludarabine at 30 mg/m2/day from days − 9 to − 5, intravenous anti-thymocyte globulin (ATG) at 15 mg/kg/day on day − 4, and intravenous Busulfan at 0.8 mg/kg on days -6 and -7 for 6 dose (total 4.8 mg/kg). Methotrexate (10 mg/m2, on days + 1, + 3, + 6, and + 11) was administered as GVHD prophylaxis. To prevent post-transplantation relapse, the patient received three additional doses of 5 × 10⁶ activated CD56⁺ cells per kilogram of body weight on days + 7, + 14, and + 21 post-transplant (Fig. 1). She was engrafted promptly at day + 9 (defined as the first of three consecutive days with an absolute neutrophil count ≥ 500/µL without G-CSF administration) for neutrophils and at day 10 for platelets (defined as the first of three consecutive days with platelet count ≥ 20,000/µL without platelet transfusion), with donor chimerism above 95% at day 100. Post-transplant CD56⁺ cell infusions were also well tolerated, with no adverse events or GVHD observed. Flow cytometric assessment of minimal residual disease (MRD) on days 30 and 90 following HSCT revealed negative results at both time points. At the last 18-month follow-up, the patient remained in complete remission, with no evidence of disease recurrence or treatment-related complications.
Discussion
Patients with FA have a significantly elevated risk of hematologic malignancies, with a cumulative risk of developing MDS or AML by the age of 40 years estimated to be 30–40% (Quentin et al. 2011). These are mainly caused by clonal karyotypic abnormalities and unbalanced translocations that result in a change in chromosome number, with the most common ones being 1q+ , 3q+ , cryptic RUNX1, and 7q- (Dufour and Pierri 2022). Although trials of lentiviral-based gene therapy are currently underway for FA patients, HSCT remains the only standard treatment for FA patients with BMF or overt MDS/AML (Martínez-Balsalobre et al. 2023). Patients with FA exhibit heightened sensitivity to chemotherapy and radiotherapy. Consequently, the primary challenge in managing MDS/AML in these individuals lies in balancing the toxicity of pre-transplant cytoreductive regimens against the risk of disease relapse (Mitchell et al. 2014).
Evidence suggests that in FA, the intrinsic aggressiveness of malignant cells may induce tissue damage, thereby exacerbating transplant-related complications. Furthermore, persistent disease activity at the time of transplantation correlates with poorer clinical outcomes and significantly higher risk of post-transplant adverse effects (Giardino et al. 2020). In a retrospective study on transformed FA patients (n = 74) undergoing allo-HSCT, Giardino et al. showed better OS outcomes in patients achieving CR before transplantation compared to recipients with active disease at the time of transplant (Giardino et al. 2020). Regarding disease reduction before HCT, various regimens, including reduced-intensity FLAG, high-dose cytarabine plus FLAG, and azacitidine, have been employed in AML/MDS transformed FA patients (Debureaux et al. 2021; Aoki et al. 2016; Ding et al. 2017); however, a high rate of fungal and viral infections has been reported specifically following the use of FLAG regimens (Debureaux et al. 2021). In this study, we explored an alternative approach by employing activated allogeneic CD56+ cells as a bridging therapy to HCT in an AML-transformed FA patient.
Anzeige
Despite other studies that employed a two-step method (CD3 depletion and CD56 enrichment) and used pure NK cells, we opted for a single-step purification (CD56 enrichment) to utilize both NK and NKT cells in evaluating the effect of GVL on leukemia cells. Given the well-documented quantitative and functional impairments of NK cells in FA patients (5), we hypothesized that the adoptive transfer of NK cells from a KIR-ligand-mismatched donor could serve as an effective immunotherapeutic bridge to HSCT. To test this hypothesis, we infused escalating doses of IL-15 activated CD56⁺ cells following a low-intensity FLAG chemotherapy regimen in a patient with transformed AML. This intervention resulted in a notable reduction in peripheral blast counts, enabling the patient to become eligible for subsequent HSCT. To our knowledge, this is the first reported case utilizing CD56+ cell therapy as a bridging strategy in a patient with FA-AML. Nevertheless, over the last years, several clinical trials have demonstrated that adoptive NK cell therapy can elicit measurable anti-leukemic responses in non-FA AML patients. For example, Björklund et al. showed that infusion of IL-2-activated haploidentical NK cells following a lymphodepleting regimen of fludarabine, cyclophosphamide, and total lymphoid irradiation led to the reduction of leukemic clones and facilitated subsequent HSCT in high-risk AML/MDS patients (Björklund et al. 2018). Pre-emptive (prophylactic) infusion of donor-derived NK cells has also been explored as a strategy to prevent relapse following HSCT in patients with AML. A recent meta-analysis reported encouraging outcomes associated with this approach, including a one-year overall survival rate of 69% and an overall response rate of 77%. The incidence of disease relapse was 28%, while acute and chronic GVHD occurred in 25% and 4% of patients, respectively (Park et al. 2024). In line with these promising findings, we also administered three escalating doses of CD56⁺ cells as prophylaxis following HSCT in our patient. Remarkably, the infusions were well tolerated, with no signs of GVHD and disease progression during follow-up. These findings suggest that prophylactic infusion of CD56+ cells may confer a protective effect in this high-risk patient population. The mechanisms and predictive factors for controlling disease progression after HSCT by CD56+ cells are still unclear. The donor-derived CD56+ cells infused in this study demonstrated potent in vitro cytotoxicity against K562 cells, along with increased surface expression of activating receptors, such as CD25 and CD69, following interleukin-15 stimulation. This suggests that their direct in-vivo cytotoxic activity against residual leukemic cells may have played a key role in the observed anti-leukemic effect. The anti-leukemic activity observed in our study may also be partly attributable to NKT cells, which remained in the final product following single-step CD56+ selection. NKT cells are a specialized subset of T lymphocytes that possess innate-like immune properties and express the CD3 and CD56 surface markers. NKT cells exhibit intense and preferential homing to the bone marrow, facilitated by high surface expression of bone marrow-homing chemokine receptors such as CXCR4 and CCR5. This property enables NKT cells to migrate to sites of malignant myeloid cell accumulation effectively and directly target these cells. Their sustained presence within the bone marrow not only enhances cytotoxic immune responses but may also contribute to the establishment of long-term immune surveillance, which is critical for preventing disease progression in conditions such as AML and MDS (Li et al. 2025). Moreover, despite their lower numbers compared with regulatory T cells (Tregs), NKT cells can suppress alloimmune responses and prevent GVHD following allo-HSCT in preclinical models (Schneidawind et al. 2013). In a study by Jaiswal et al. the feasibility and safety of infusing unactivated CD56⁺ cells following allo-HSCT were evaluated. Donor-derived NK and NKT cells were isolated using a single-step CD56⁺ selection method and then administered to patients with advanced myeloid malignancies one week post-transplant. The reported mean doses of CD56⁺, CD3⁻, and CD56⁺CD3⁺ cells were 6.7 × 10⁶/kg and 1.15 × 10⁶/kg, respectively. Preliminary findings indicated that this approach was associated with accelerated hematopoietic engraftment, improved reconstitution of CD4⁺ T cells, regulatory T cells, and NK cells, as well as a reduced incidence of acute GVHD (Jaiswal et al. 2017). However, in our study, we employed a multi-dose regimen of CD56⁺ cell infusions administered on days + 7, + 14, and + 21 post-transplant. In addition, a higher number of NKT cells was infused, and the cells were pre-activated with IL-15 to enhance their functional capacity and in vivo persistence.
In conclusion, this case report describes the first use of CD56+ cell immunotherapy, pre- and post-transplant, in a patient with transformed AML. The clinical outcome demonstrated that activated CD56+ cell therapy was safe and effective in treating this patient. However, further studies with larger patient cohorts and longer follow-up periods are necessary to validate these findings and to better understand the therapeutic potential and long-term safety of CD56+ cell immunotherapy in this context.
Acknowledgements
The authors thank Shahid Beheshti University of Medical Sciences (Tehran, Iran) for its support of this study.
Declarations
Conflict of interest
The authors declare they have no Conflict of interest or financial relationships to disclose.
Anzeige
Consent for publication
Not applicable.
Ethical approval
Not applicable.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Aoki T, Koh K, Ikeda Y, Sekinaka Y, Akiyama K, Mori M et al (2016) Addition of high-dose cytarabine to fludarabine-based conditioning for hematopoietic stem cell transplantation for treating Fanconi Anemia patients with advanced myeloid malignancy: a single-center experience and literature review. Biol Blood Marrow Transplant 22(9):1725–1728CrossRefPubMed
Björklund AT, Carlsten M, Sohlberg E, Liu LL, Clancy T, Karimi M et al (2018) Complete remission with reduction of high-risk clones following haploidentical NK-cell therapy against MDS and AML. Clin Cancer Res 24(8):1834–1844CrossRefPubMed
Cooley S, He F, Bachanova V, Vercellotti GM, DeFor TE, Curtsinger J et al (2017) Neurological consequences of cytokine release syndrome following subcutaneous recombinant IL-15 and haploidentical donor natural killer cell therapy for advanced acute myeloid leukemia. Blood 130:2649
de Latour RP, Soulier J (2016) How I treat MDS and AML in Fanconi anemia. Blood 127(24):2971–2979CrossRef
de Latour RP, Porcher R, Dalle JH, Aljurf M, Korthof ET, Svahn J et al (2013) Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European group for blood and marrow transplantation experience. Blood 122(26):4279–4286CrossRef
Debureaux PE, Sicre de Fontbrune F, Bonfim C, Dalle JH, Buchbinder N, Bertrand Y, Renard C, Forcade E, Fernandes J, Talbot A, Pasquini R (2021) FLAG-sequential regimen followed by bone marrow transplantation for myelodysplastic syndrome or acute leukemia in patients with Fanconi anemia: a Franco-Brazilian study. Bone Marrow Transpl 56(1): 285–288
Ding H, Hashem H, Cabral L, Rangarajan H, Abusin G, Lazarus HM, Abu-Arja R (2017) Azacitidine as a bridge to allogeneic hematopoietic cell transplantation in a pediatric patient with Fanconi anemia and acute myeloid leukemia. Pediatric Transpl 21(2):e12870CrossRef
Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H et al (2022) Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 140(12):1345–1377CrossRefPubMed
Dufour C, Pierri F (2022) Modern management of Fanconi Anemia. Hematology Am Soc Hematol Educ Program 2022(1):649–657CrossRefPubMedPubMedCentral
Eghbali A, Safdari SM, Yousefi Roozbahani M, Tavajohi K, Hosseini S (2024) Fanconi Anemia: challenges in diagnosis and management—a case series report. Clin Case Rep 12(11):e9583CrossRefPubMedPubMedCentral
Giardino S, de Latour RP, Aljurf M, Eikema DJ, Bosman P, Bertrand Y et al (2020) Outcome of patients with Fanconi Anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: a retrospective analysis on behalf of EBMT group. Am J Hematol 95(7):809–816CrossRefPubMed
Hashemi E, Bjorgaard S, Wang D, Uyemura B, Riese M, Thakar MS et al (2021) NK cell development and function in patients with Fanconi Anemia. Crit Rev Immunol 41(2):35–44CrossRefPubMedPubMedCentral
Jaiswal SR, Zaman S, Nedunchezhian M, Chakrabarti A, Bhakuni P, Ahmed M et al (2017) CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease: a pilot study. Cytotherapy 19(4):531–542CrossRefPubMed
Justo GA, Bitencourt MA, Pasquini R, Castelo-Branco MT, Almeida-Oliveira A, Diamond HR et al (2014) Immune status of Fanconi anemia patients: decrease in T CD8 and CD56dim CD16+ NK lymphocytes. Ann Hematol 93(5):761–767CrossRefPubMed
Lee KH, Yoon SR, Gong JR, Choi EJ, Kim HS, Park CJ et al (2023) The infusion of ex vivo, interleukin-15 and -21-activated donor NK cells after haploidentical HCT in high-risk AML and MDS patients—a randomized trial. Leukemia 37(4):807–819CrossRefPubMed
Li YR, Fang Y, Niu S, Zhu Y, Chen Y, Lyu Z et al (2025) Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies. Nat Commun 16(1):1248CrossRefPubMedPubMedCentral
Martinez-Balsalobre E, Guervilly JH, van Asbeck-van der Wijst J, Perez-Oliva AB, Lachaud C (2023) Beyond current treatment of Fanconi Anemia: what do advances in cell and gene-based approaches offer?. Blood Rev 60: 101094
Mehta PA, Emoto C, Fukuda T, Seyboth B, Teusink-Cross A, Davies SM et al (2019) Busulfan pharmacokinetics and precision dosing: are patients with Fanconi Anemia different? Biol Blood Marrow Transplant 25(12):2416–2421CrossRefPubMedPubMedCentral
Mitchell R, Wagner JE, Hirsch B, DeFor TE, Zierhut H, MacMillan ML (2014) Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi Anemia. Br J Haematol 164(3):384–395CrossRefPubMed
Myers KC, Sauter S, Zhang X, Bleesing JJ, Davies SM, Wells SI, Mehta PA, Kumar A, Marmer D, Marsh R, Brown D (2017) Impaired immune function in children and adults with Fanconi anemia. Pediatric Blood Cancer 64(11):e26599CrossRef
Park H, Kim G, Kim N, Ha S, Yim H (2024) Efficacy and safety of natural killer cell therapy in patients with solid tumors: a systematic review and meta-analysis. Front Immunol 15:1454427CrossRefPubMedPubMedCentral
Quentin S, Cuccuini W, Ceccaldi R, Nibourel O, Pondarre C, Pagès MP et al (2011) Myelodysplasia and leukemia of Fanconi Anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions. Blood 117(15):e161–e170CrossRefPubMed
Schneidawind D, Pierini A, Negrin RS (2013) Regulatory T cells and natural killer T cells for modulation of GVHD following allogeneic hematopoietic cell transplantation. Blood 122(18):3116–3121CrossRefPubMedPubMedCentral
Der Umgang mit Zufallsentdeckungen ist ein vieldiskutiertes Thema im Zusammenhang mit dem Low-Dose-CT-Screening auf Lungenkrebs. Eine Studie hat sich nun speziell mit inzidentellen Befunden befasst, die auf ein extrapulmonales Malignom verdächtig sind.
Medizinischen Rat von Chatbots auf der Basis sogenannter künstlicher Intelligenz haben laut Umfragen bereits knapp die Hälfte aller Erwachsenen schon einmal eingeholt. Welche Chancen und Risiken birgt das?
Wie sinnvoll ist es, bei Menschen jenseits der 75 nach Entfernung eines Adenoms Überwachungskoloskopien durchzuführen? Eine große US-Kohortenstudie zeigt: Das Darmkrebsrisiko war nach zehn Jahren sehr gering, ob mit oder ohne Polypektomie in der Vorgeschichte. Bei weitem höher war das Risiko, an einer anderen Erkrankung zu versterben.
Die körperliche Aktivität zu steigern – das scheint das Leben von Frauen mit Brustkrebs auf Basis eine Modellrechnung deutlich zu verlängern. Wie sie aber mehr Bewegung erreichen können, bleibt offen.
