Clinical features and outcomes of patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia: a multicentre, retrospective, cohort study

This study aimed to investigate the clinical features and outcomes of patients with myelodysplastic syndrome or acute myeloid leukaemia and Shwachman-Diamond syndrome, an inherited bone marrow failure disorder with high risk of developing myeloid malignancies.MethodsWe did a multicentre, retrospective, cohort study in collaboration with the North American Shwachman-Diamond Syndrome Registry. We reviewed patient medical records from 17 centres in the USA and Canada. Patients with a genetic (biallelic mutations in the SBDS gene) or clinical diagnosis (cytopenias and pancreatic dysfunction) of Shwachman-Diamond syndrome who developed myelodysplastic syndrome or acute myeloid leukaemia were eligible without additional restriction. Medical records were reviewed between March 1, 2001, and Oct 5, 2017. Masked central review of bone marrow pathology was done if available to confirm leukaemia or myelodysplastic syndrome diagnosis. We describe the clinical features and overall survival of these patients.FindingsWe initially identified 37 patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia. 27 patients had samples available for central pathology review and were reclassified accordingly (central diagnosis concurred with local in 15 [56%] cases), 10 had no samples available and were classified based on the local review data, and 1 patient was excluded at this stage as not eligible. 36 patients were included in the analysis, of whom 10 (28%) ini...
Source: The Lancet Haematology - Category: Hematology Source Type: research

Related Links:

Rationale: The success of tyrosine kinase inhibitor (TKI) therapy has greatly prolonged the survival time of patients with chronic myeloid leukemia (CML), harboring the characteristic Philadelphia (Ph) chromosome. However, a fraction of patients, achieving complete cytogenetic response after TKI therapy, develop a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with additional clonal chromosomal abnormalities in Philadelphia-negative cells (CCA/Ph–). Patient concerns: A 56-year-old woman with AML, developing from Philadelphia-negative CML after TKI therapy. She showed 6 kinds of somatic variants&m...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15–20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone marrow, or defining cytogenetic abnormalities. Laboratory diagnoses of myelodysplastic syndromes (MDS) depend on morphological changes based on dysplasia in peripheral blood and bone marrow, including peripheral blood smears, bone marrow aspirate smears, and bone marrow biopsies. As leukemic cells are not functional, the patient develops anemia, neutropenia, and thrombocytopenia, leading to fatigue, recurrent infections, and hemorrhage. The genetic b...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsDLI was associated with a durable efficacy and low toxicity in pediatric patients with hematologic malignancies. However, larger studies and standardized approaches are required to identify the outcome predictors of this treatment modality.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 7 August 2019Source: The Lancet HaematologyAuthor(s): Farhad Ravandi, Rita Assi, Naval Daver, Christopher B Benton, Tapan Kadia, Philip A Thompson, Gautam Borthakur, Yesid Alvarado, Elias J Jabbour, Marina Konopleva, Koichi Takahashi, Steven Kornblau, Courtney D DiNardo, Zeev Estrov, Wilmer Flores, Sreyashi Basu, James Allison, Padmanee Sharma, Sherry Pierce, Allison PikeSummaryBackgroundOutcomes for younger patients with acute myeloid leukaemia have moderately improved over the past two decades owing to better supportive care and recent introduction of novel targeted agents. Blocking PD-...
Source: The Lancet Haematology - Category: Hematology Source Type: research
Allogeneic hematopoietic cell transplantation (HCT) is the most potent postremission therapy in patients with acute myelogenous leukemia (AML) [1,2], and is widely used in younger patients with intermediate-risk or adverse-risk cytogenetics [3]. Transplantation decisions are based mainly on cytogenetic and molecular risk group, age, comorbidity, response to therapy, and the availability of a suitable donor [4]. AML is secondary (s-AML) in more than 25% of all cases, arising after previous chemotherapy and/or radiotherapy (i.e., therapy-related [t-AML]) or developing after an antecedent myeloid disease (AHD-AML), such as my...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a distinct entity defined by the World Health Organization (WHO) in 2008, by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or a history of MDS or MDS/myeloproliferative neoplasm (MPN) [1]. In the 2016 WHO classification, AML-MRC was preserved as a distinct entity, with some minor revisions in MDS-related cytogenetics [2]. A majority of the patients in studies reporting that the prognosis of AML-MRC was worse than that of AML-not otherwise specified (NOS) [3 –8] had undergone chemothe...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Conclusions 1. For the first time rejuvenation therapy was started so late, at the point when half of the animals had already died, and the high (31 ± 5%) extension in maximal lifespan of the remaining animals was found. such significant effect on the maximal lifespan, unlike the median lifespan fluctuations, indicates that BM transplantation affects the intrinsic aging mechanism. The life-extending effect was significantly stronger than in earlier works with similar design (no irradiation or chemotherapy, no hereditary pathologies in recipients, advanced age at the start of the BM administration) because of (i) th...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
This study proposed a pilot study of a new tool for a reliable and accurate stratification of patients with acute leukemia based on an integrative model of leukemia behavior, cell characterization, and clinical features, in addition, to an evaluation of intra-tumor and inter-tumor heterogeneity. Together our approach allows us to introduce an integrative quantitative approach to use zebrafish and tumor characterization as a prediction tool for the behavior of acute leukemia in young adults. Materials and Methods Animal Care and Handling Zebrafish wild-type (A/B and TAB5) adults were raised and maintained according to st...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Bewersdorf JP, Stahl M, Zeidan AM Abstract INTRODUCTION: Immune system evasion is essential for tumor cell survival and is mediated by the immunosuppressive tumor microenvironment and the activation of inhibitory immune checkpoints. While immune checkpoint-based therapy yielded impressive results in several advanced solid malignancies such as melanoma and non-small cell lung cancer, its role in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is still evolving. Areas covered: Here we review the immunology in the tumor microenvironment in the bone marrow and discuss the current preclinical an...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia derived from MDS (sAML) [1,2]. However, there is controversy among experts if and how patients with MDS should receive cytoreductive “debulking” chemotherapy before transplant. MDS patients without elevated bone marrow blast counts usually proceed to transplant without cytoreduction, whereas patients with MDS and excess blasts and those with sAML often receive cytoreductive treatment in order to achieve remission before trans plant [1,3].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
More News: Acute Leukemia | Acute Myeloid Leukemia | Canada Health | Cancer & Oncology | Chemotherapy | Genetics | Hematology | Leukemia | Myelodysplastic Syndrome | Pancreas | Pathology | Stem Cell Therapy | Stem Cells | Study | Toxicology | Transplants | USA Health