Exploring blast composition in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms: CD45RA and CD371 improve diagnostic value of flow cytometry through assessment of myeloblast heterogeneity and stem cell aberrancy

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are haematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) that display a paradoxical bone marrow phenotype hallmarked by myeloid proliferation in the context of bone marrow dysplasia and ineffective haematopoiesis. The unfolding MDS/MPN genomic landscape has revealed numerous mutations in signalling genes, such as CBL, JAK2, NRAS, KRAS, CSF3R, and others involving the spliceosome complex. These observations suggest that comutation of genes involved in dysplasia and bone marrow failure along with those of cytokine receptor signalling may, in part, explain the dual MDS/MPN phenotype. The respective MDS/MPN diseases are identified by the type of myeloid subset which predominates in the peripheral blood. Currently there are no standard treatment recommendations for most patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic endpoints and standardized response criteria for clinical trials.

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Diagnostic Value of Flow Cytometry Standardized Using the European LeukemiaNet for Myelodysplastic Syndrome

Acta Haematologica ◽

10.1159/000501147 ◽

2019 ◽

Vol 143 (2) ◽

pp. 140-145 ◽

Cited By ~ 1

Author(s):

Akihiro Takeuchi ◽

Osamu Imataki ◽

Hiroyuki Kubo ◽

Akihiro Kondo ◽

Kayoko Seo ◽

...

Keyword(s):

Flow Cytometry ◽

Myeloproliferative Neoplasms ◽

Diagnostic Value ◽

Morphological Examination ◽

Valuable Alternative ◽

Ringed Sideroblasts ◽

Hematological Disorders ◽

Low Incidence ◽

Low Sensitivity ◽

Undetermined Significance

Background: Myelodysplastic syndromes (MDS) and idiopathic cytopenia of undetermined significance (ICUS) are heterogeneous hematological disorders characterized by hematopoietic dysplasia and/or chromosomal aberrancy. Objectives: This study aimed to evaluate the diagnostic value of flow cytometry standardized using the European LeukemiaNet (ELN) for MDS and ICUS by analyzing samples obtained from patients with cytopenia based on morphological examination, cytogenetic analysis, and flow cytometry. Methods: We retrospectively analyzed bone marrow samples aspirated from 253 consecutive patients (median age: 66 years [range: 1–92]) to identify the cause of cytopenia. Results: Sixty patients presented with MDS, and 16 with ICUS. MDS subtypes were distributed as follows: MDS with single-lineage dysplasia (n = 10); MDS with multi-lineage dysplasia (n = 10); MDS with ringed sideroblasts (n = 4); MDS with excess blasts-1 (n = 9); MDS with excess blasts-2 (n = 13), MDS unclassified (n = 5); 5q-syndrome (n = 6); and MDS/myeloproliferative neoplasms (n = 3). Four representative ELN indexes were used. Two or more ELN MDS indexes were in the abnormal range in 35 MDS cases (58.3%) and 4 ICUS cases (25.0%). Conclusions: Morphological examination remains the standard for MDS diagnosis. Considering the low incidence of genetically proven ICUS (20.2–27.5%), the low sensitivity of ELN MDS indexes for ICUS is considered a valuable alternative.

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Multiparameter flow cytometry for assessment of minimal residual disease in patients with myelodysplastic syndromes treated with allogeneic stem cell transplantation

Acta Haematologica Polonica ◽

10.2478/ahp-2020-0017 ◽

2020 ◽

Vol 51 (2) ◽

pp. 88-94

Author(s):

Katarzyna Wiśniewska-Piąty ◽

Joanna Dziaczkowska-Suszek ◽

Agata Wieczorkiewicz-Kabut ◽

Karolina Chromik ◽

Anna Koclęga ◽

...

Keyword(s):

Flow Cytometry ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Minimal Residual Disease ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Myelodysplastic Syndromes ◽

Residual Disease ◽

Multiparameter Flow Cytometry ◽

Minimal Residual

AbstractBackgroundMyelodysplastic syndromes (MDSs) are a heterogeneous group of clonal myeloid neoplasms. Allogeneic stem cell transplantation (allo-SCT) remains the curative method for MDS treatment. Little is known about the monitoring of minimal residual disease (MRD) in patients with MDS after allo-SCT.AimWe aimed to evaluate the significance of leukemia-associated immunophenotypes (LAIPs) identified in acute myeloid leukemia (AML) for MRD monitoring in patients with MDS after allo-SCT.Material and methodsSeven males and 4 females with a median age of 55 years were included. The diagnosis of MDS was established according to 2016 World Health Organization (WHO) criteria. The significance of eight LAIPs in bone marrow samples using multiparameter flow cytometry (MFC) was evaluated for MRD.ResultsEight patients were positive for several LAIPs before allo-SCT. The identified LAIPs included the presence of aberrant lymphoid antigens on myeloblasts and lack of CD33 expression on myeloblasts. All studied MDS patients were negative for LAIPs at Day +30 after the procedure. This was followed by full-donor chimerism in all cases. The Ogata score after allo-SCT decreased in all patients in whom it was indicative for MDS before allo-SCT.ConclusionsMFC could be useful in monitoring MRD in MDS patients after allo-SCT. Further studies in this field are needed.

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The Diagnostic Role of Flow Cytometry in Idiopathic Cytopenia of Unknown Significance (ICUS): A Single-Center Analysis of 79 Patients

Blood ◽

10.1182/blood-2018-99-114517 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3105-3105

Author(s):

Konstantinos Dimopoulos ◽

Olga Kristina Hansen ◽

Jakob Werner Hansen ◽

Lene Sjö ◽

Leonie Saft ◽

...

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

Board Of Directors ◽

Myelodysplastic Syndromes ◽

Diagnostic Value ◽

Low Grade ◽

Severe Dysplasia ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Flow Cytometric

Abstract Introduction and aims The term ICUS is used to describe cases with persistent cytopenia (more than 6 months) without evidence of dysplasia in the bone marrow (BM) smear, and normal cytogenetics. Flow cytometry is currently a standard tool for the diagnosis of myelodysplastic syndromes (1). Our goal was to evaluate the efficacy of flow cytometry in detecting bone marrow dysplasia in the absence of abnormal morphology. Materials and methods A total of 79 patients with ICUS and 12 patients with MDS were analyzed with a standardized flow cytometry panel (2). Data were analyzed using two different algorithms; the Ogata algorithm (3) and Wells algorithm (4). For each of the algorithms, samples were classified as suggestive for dysplasia when scoring equal to or higher than 2. Furthermore, all ICUS patients were screened for mutations using targeted sequencing of 20 genes (DNMT31, TET2, EZH2, SRSF2, CBL1, SF3B1, UAF1, GATA2, IDH1, IDH2, CEBPa1, ZRSR2, TP53, KRAS, NRAS, ETV6, RUNX1, JAK2 and ASXL1) and 57/71 samples were additionally evaluated for signs of dysplasia by two independent hematopathologists. Results The diagnostic value of flow cytometry in MDS was confirmed by our data; the Wells algorithm was slightly superior to Ogata algorithm in predicting MDS (10/12 patients (83.3%) vs. 7/12 patients (58.3%) respectively, fig. 1A) and was therefore the main algorithm used for the further analysis of the ICUS patients. Flow cytometry was suggestive of dysplasia in 34/79 (43%) patients with ICUS. Interestingly, in patients with at least one detected mutation, flow cytometry was positive in 23/42 (54.8%) of the cases, while it was positive in 8/9 (88.9%) patients with more than two mutations (fig. 1C). There was no higher frequency of abnormal flow cytometry in patients with higher risk mutations. Additionally, for the 57 patients evaluated for dysplastic changes, flow cytometric abnormalities were more frequent (p= 0.05) in the 22 patients with moderate/severe dysplasia (15/22 patients or 68.2%, fig. 1D). After a median follow-up of 20 months (range: 3 - 90), a total of eight patients progressed to either MDS, CMML or AML. Interestingly, these eight patients had flow cytometric abnormalities suggestive of dysplasia before developing hematological malignancy. In conclusion, flow cytometry can identify a subgroup of ICUs patients with a higher mutational burden, dysplastic changes and a higher risk for progression to MDS or a more aggressive myeloid disease and has a place in the diagnostic evaluation of patients with idiopathic cytopenia. References: Porwit A, Van De Loosdrecht AA, Bettelheim P, Eidenschink Brodersen L, Burbury K, Cremers E, et al. Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes - Proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS. Leukemia. 2014;28(9):1793-8. van Dongen JJM, Lhermitte L, Böttcher S, Almeida J, van der Velden VHJ, Flores-Montero J, et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia [Internet]. 2012 Sep [cited 2014 Nov 28];26(9):1908-75. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3437410&tool=pmcentrez&rendertype=abstract Porta MGD, Picone C, Pascutto C, Malcovati L, Tamura H, Handa H, et al. Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: Results of a European LeukemiaNET study. Haematologica. 2012;97(8):1209-17. Wells DA, Benesch M, Loken MR, Vallejo C, Myerson D, Leisenring WM, et al. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood. 2003;102(1):394-403. Figure 1. Figure 1. Disclosures Hansen: Otsuka Pharma: Membership on an entity's Board of Directors or advisory committees. Grønbæk:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen Pharma: Membership on an entity's Board of Directors or advisory committees; Otsuka Pharma: Membership on an entity's Board of Directors or advisory committees.

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Quantitative Analysis of Flow Cytometry Immunophenotyping Data for Aiding in the Diagnosis of Myelodysplastic Syndromes (MDS).

Blood ◽

10.1182/blood.v104.11.4735.4735 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4735-4735

Author(s):

Ha T. Nishino ◽

Youli Zu ◽

Larry Rice ◽

Kelty R. Baker ◽

John J. McCarthy ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Stem Cell ◽

Quantitative Analysis ◽

Stem Cell Transplantation ◽

Myelodysplastic Syndromes ◽

De Novo ◽

Glycophorin A ◽

Erythroid Precursors ◽

De Novo Aml

Abstract Recent studies have shown that flow cytometry immunophenotyping is a promising tool aiding in the diagnosis of myelodysplastic syndromes (MDS). However, the majority of these studies apply only qualitative pattern analysis in their interpretation of immunophenotypic data. The goal of this study was to analyze immunophenotyping results quantitatively, investigating the potential of this approach for providing additional information useful diagnosing MDS. Using flow cytometry immunophenotyping, we studied 56 bone marrow specimens from 13 patients with well-defined MDS by morphologic, clinical, and/or cytogenetic findings (5 RA, 3 RARS, 2 RAEB grade 1, 2 RAEB grade 2 and 1 secondary to chemotherapy), 15 cytopenic patients (controls, age-matched with MDS patients) with non-MDS/non-clonal hematologic disorders receiving marrow evaluation for other reason (ITP, fever of unknown origin, or lymphoma staging), 8 patients with AML transformed from MDS (t-AML), 6 patients with de novo AML, and 7 patients (14 specimens) with regenerating marrow after stem cell transplantation. These samples were analyzed qualitatively as reported in the literature as well as quantitatively for percentages of T-cells (CD3+), B-cells (CD20+), NK cells (CD3−/CD56+), granulocytes (moderate CD45 intensity and high side scatter characteristics), monocytes (CD14+/CD11c+), blasts (defined by dim CD45 and low side scatter, CD34+ or CD117+), erythroid precursors (CD71+/CD45−) and plasma cells (bright CD38), CD4/CD8 ratio, percentages of granulocyte subsets (CD10+, CD10−, CD36+/CD64+, CD36−/CD64+, CD11b−/CD16−, CD11b+/CD16− or CD11b+/CD16+ granulocytes per total granulocytes), percentage of CD56+ monocytes, and percentages of erythorid precursors subset (glycophorin A+ or glycophorin A- erythroid precursors per total erythroid precursors). In agreement with previous studies, qualitative analysis of these data demonstrated abnormal patterns of expression in myeloid and erythroid lineages in patients with MDS and t-AML. However, these patterns are also observed in age-matched controls and patients with de novo AML or with regenerating marrow. The quantitative analysis showed significantly increased T-cells and a significantly decreased granulocyte subset of CD11b+/CD16− in MDS patients when compared to age-matched controls (9.0 +/− 6.7% vs. 4.4 +/− 3.0 %, p = 0.023 and 28.1 +/− 14.9% vs. 44.5 +/−12.9%, p = 0.004, student t-test). There were also trends for increased NK cells and CD4:CD8 ratios and decreased total granulocytes in MDS patients as compared to the age-matched controls (p = 0.097, 0.094 and 0.059, respectively, student t-test). Other immunophenotypic parameters demonstrated no significant differences between these two groups. Furthermore, the changes observed in MDS patients were also seen in patients with t-AML. Patients with de novo AML or regenerating marrow post stem cell transplantation showed a quantitative immunophenotypic pattern between that of MDS patients and age-matched controls. These findings suggest that quantitative analysis of flow cytometry immunophenotyping data can aid in the diagnosis in MDS as well as the identification of AML arising from background MDS. The latter is clinically significant since these patients carry worse prognosis than those with de novo AML and may require novel therapies.

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Diverse Genetic Lesions In Myelodysplastic Syndromes Originate Exclusively In Rare MDS Stem Cells

Blood ◽

10.1182/blood.v122.21.4195.4195 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4195-4195

Author(s):

Petter Woll ◽

Una Kjällquist ◽

Onima Chowdhury ◽

Rikard Erlandsson ◽

Helen Doolittle ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Bone Marrow ◽

Flow Cytometry ◽

Stem Cell ◽

Myelodysplastic Syndromes ◽

Intermediate Risk ◽

Self Renewal ◽

Nsg Mice ◽

Unique Ability

Abstract Background The popular concept that human cancers might be driven by rare self-renewing cancer stem cells (CSCs) has extensive implications for cancer biology and modelling, as well for development of more efficient and targeted therapies. However, experimental support for the existence of distinct and rare CSCs in human malignancies remain contentious, particularly in light of compelling evidence that cancer-propagating cells frequently fail to read out in existing human stem cell assays. Therefore, to unequivocally establish the existence and identity of human CSCs, the challenge is first to identify candidate CSCs, and to establish their unique ability to self-renew and replenish molecularly and functionally distinct non-tumorigenic progeny followed by functional in situ validation within the patients themselves. Methods We have in the hematological malignancy myelodysplastic syndromes (MDS) characterize candidate hematopoietic stem and progenitor stages in the bone marrow of low-intermediate risk MDS patients by flow cytometry. Distinct cell populations were functionally characterised for lineage commitment in standard colony forming cell (CFC) assays, and for self-renewal potential in long-term culture initiating cell (LTC-IC) assays and in immune-deficient (NSG) mice. Moreover, we tracked the cellular origin of all identified somatic genetic lesions identified in each patient by targeted next-generation sequencing of genomic DNA isolated from each purified MDS stem and progenitor cell population. Results In low-intermediate risk MDS patients, regardless whether they were del(5q) (n=19) or non-del(5q) (n=11), we could identify rare but distinct Lin-CD34+CD38-CD90+CD45RA- candidate stem cells, granuclocyte-monocyte progenitors (GMPs) and megakaryocyte-erythroid progenitors (MEPs) with frequencies within total BM similar to that of normal age-matched controls. Global gene expression analysis by RNA sequencing of MDS stem cells, GMPs and MEPs suggested that these are molecularly distinct populations. Myeloid and erythroid gene expression signatures were restricted to the GMPs and MEPs, respectively, whereas a transcriptional stem cell signature was restricted to the MDS stem cells. GMPs and MEPs isolated from del(5q) (n=12) and non-del(5q) (n=8) MDS patients displayed lineage-restricted myeloid and erythroid differentiation potentials, respectively. Self-renewal in LTC-IC assay was restricted exclusively to MDS Lin-CD34+CD38-CD90+CD45RA- stem cells in del(5q) (n=11) and non-del(5q) (n=8) MDS patients. Xenotransplantation into NSG mice also confirmed that only Lin-CD34+CD38-CD90+CD45RA- MDS stem cells have in vivo self-renewal potential, and these experiments also demonstrated their ability to replenish downstream CMPs, GMPs and MEPs, establishing the hierarchical relationship of MDS stem and progenitor cells. Targeted DNA sequencing of 88 genes recurrently mutated in MDS and other myeloid malignancies was pursued to identify somatic genetic lesions within the bulk bone marrow of MDS patients (n=13). In total we identified 30 presumed genetic driver lesions, including del(5q) and mutations in key transcription factors (RUNX1), signalling pathways (JAK2, CSF3R), epigenetic regulators (TET2, ASXL1), apoptosis regulators (TP53), and spliceosome components (SF3B1, SRSF2, U2AF2, SRSF6). Importantly, in support of their unique ability to self-renew and replenish lineage-restricted MDS progenitors, all stable somatic genetic lesions identified could in each MDS patient be backtracked to the rare stem cell population as defined phenotypically by flow cytometry and functionally by LTC-IC or xenograft potential, unequivocally establishing their unique stem cell identity within the malignant clone. Conclusions These findings provide definitive evidence for the existence of rare and distinct stem cells in MDS, a finding with extensive implications for therapeutic strategies in MDS and other cancers whose existence might also strictly depend on the persistence of rare CSCs. MDS stem cells typically acquire multiple driver mutations, together conferring a competitive advantage over normal stem cells, while even in combination failing to inflict self-renewal ability on MDS myelo-erythroid progenitor cells. Disclosures: No relevant conflicts of interest to declare.

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An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults

Blood ◽

10.1182/blood-2014-10-607341 ◽

2015 ◽

Vol 125 (12) ◽

pp. 1857-1865 ◽

Cited By ~ 86

Author(s):

Michael R. Savona ◽

Luca Malcovati ◽

Rami Komrokji ◽

Ramon V. Tiu ◽

Tariq I. Mughal ◽

...

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Myelodysplastic Syndromes ◽

Myeloproliferative Neoplasms ◽

Response Assessment ◽

Response Criteria ◽

Treatment Algorithms ◽

International Panel ◽

Assessment Guidelines ◽

Suitable Treatment

Abstract Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation.

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09 / ALLOGENEIC STEM CELL TRANSPLANTATION IN PHILADELPHIA-NEGATIVE CHRONIC MYELOPROLIFERATIVE NEOPLASMS. A CENTER EXPERIENCE

10.26226/morressier.5b3b802db1b87b000eced94c ◽

2018 ◽

Author(s):

Avendaño Pita Alejandro

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Myeloproliferative Neoplasms ◽

Chronic Myeloproliferative Neoplasms

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Exosomes from human umbilical cord mesenchymal stem cells attenuate the inflammation of severe steroid-resistant asthma by reshaping macrophage polarization

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02244-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Bing Dong ◽

Chao Wang ◽

Jing Zhang ◽

Jinrong Zhang ◽

Yinuo Gu ◽

...

Keyword(s):

Flow Cytometry ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Quantitative Proteomics ◽

Macrophage Polarization ◽

Human Umbilical Cord ◽

Raw 264.7 ◽

Steroid Resistant ◽

Central Protein

Abstract Background Severe, steroid-resistant asthma (SSRA) is a serious clinical problem in asthma management. Affected patients have severe clinical symptoms, worsened quality of life, and do not respond to steroid, a mainstay steroid treatment of asthma. Thus, effective therapies are urgently needed. Exosomes derived from mesenchymal stem cell (MSC-Exo) has become attractive candidates for the lung inflammatory diseases through its immunomodulatory effects. In this study, we explored the therapeutic effects of MSC-Exo in SSRA and identified the therapeutic mechanism of MSC-Exo. Method Exosomes from human umbilical cord mesenchymal stem cell (hUCMSC) were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis and flow cytometry analysis. Effects of MSC-Exo on airway hyper responsiveness (AHR), inflammation, histopathology, and macrophage polarization in SSRA in mice were evaluated. Systematic depletion of macrophages determined the role of macrophages in the therapeutic effect of SSRA in mice. LPS-stimulated RAW 264.7 cell model was constructed to determine the underlying mechanism of MSC-Exo on macrophage polarization. qRT-PCR, Western blotting, immunofluorescence, and flow cytometry were performed to evaluate the expression of M1 or M2 markers. Tandem mass tags (TMT)-labeled quantitative proteomics were applied to explore the central protein during the regulation effect of MSC-Exo on macrophage polarization. Knockdown and overexpression of TRAF1 were used to further clarify the role of the central protein on macrophage polarization. Result We successfully isolated and characterized exosomes from hUCMSCs. We verified that the intratracheal administration of MSC-Exo reversed AHR, histopathology changes, and inflammation in SSRA mice. Systematic depletion of macrophages weakened the therapeutic effect of MSC-Exo. We found that MSC-Exo treatment inhibited M1 polarization and promoted M2 polarization in LPS-stimulated RAW 264.7 cells. Subsequently, tumor necrosis factor receptor-associated factor 1 (TRAF1) was determined as the central protein which may be closely related to the regulation of macrophage polarization from TMT-labeled quantitative proteomics analysis. Knockdown and overexpression of TRAF1 demonstrated that the effect of MSC-Exo treatment on macrophage polarization, NF-κB and PI3K/AKT signaling was dependent on TRAF1. Conclusion MSC-Exo can ameliorate SSRA by moderating inflammation, which is achieved by reshaping macrophage polarization via inhibition of TRAF1.

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Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001818 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001818 ◽

Cited By ~ 1

Author(s):

Chantal Saberian ◽

Noha Abdel-Wahab ◽

Ala Abudayyeh ◽

Hind Rafei ◽

Jacinth Joseph ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myelodysplastic Syndromes ◽

Myeloid Leukemia ◽

Acute Gvhd ◽

Checkpoint Inhibitors ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Gvhd Prophylaxis ◽

Acute Myeloid

BackgroundImmune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.MethodsA retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.ResultsFour patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2–4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).ConclusionsICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

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