Impact of Genetic Mutations on the Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Myeloid Leukemia with Antecedent Myeloproliferative Neoplasm

We previously demonstrated poor outcomes of patients with acute myeloid leukemia (AML) with antecedent myeloproliferative neoplasms (MPN) undergoing allogeneic hematopoietic stem cell transplantation (HCT) (Gupta et al, BBMT, 2019; abstract 140). In particular, we did not find any difference in outcomes of patients who received transplant “in remission” defined as blood and bone marrow blasts
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 12 Source Type: research

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Relapsed acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) following an allogeneic stem cell transplant has a bleak prognosis with no standard for treatment identified. Current literature suggests combining hypomethylating agents (HMA) with a donor lymphocyte infusion (DLI) as salvage therapy to reduce disease burden and induce a graft versus leukemia (GVL) effect. At our institution, this salvage therapy option is being used for this population, peaking interest in our experience to date.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 608 Source Type: research
We describe the case of a patient who presented as a teenager with thrombocytopenia and was later diagnosed with chronic myelomonocytic leukemia, with eventual transformation to acute myeloid leukemia, which has relapsed after stem cell transplantation. She was found to have short telomeres and a TERT mutation, in addition to numerous features suggestive of a germline predisposition syndrome. These findings have not been specifically associated with chronic myelomonocytic leukemia and raise interesting questions about the associations between myelodysplastic/myeloproliferative neoplasms, telomere biology disorders, and the...
Source: Pathology Case Reviews - Category: Pathology Tags: Case Reviews Source Type: research
This article reviews management considerations for the advanced-phase MPNs (MPN-AP and MPN-BP), with a special focus on MPN-AP, and highlights novel experimental therapies. PMID: 31449507 [PubMed - in process]
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research
Allogeneic hematopoietic cell transplantation (HCT) is the most potent postremission therapy in AML [1, 2], and is widely used in younger patients with intermediate or adverse risk cytogenetics [3]. Transplant decisions are mainly based on the cytogenetic and molecular risk group, age, comorbidity, response to therapy and on the availability of a suitable donor [4]. AML is in more than one fourth of all cases secondary (s-AML), arising after previous chemo- and/or radiotherapy, i.e., therapy-related (t-AML), or developing after an antecedent myeloid disease (AHD-AML), such as myelodysplastic syndromes (MDS) or myeloprolife...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: 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 The discovery of JAK2V617F mutation in BCR-ABL1-negative MPNs by four different international cooperative groups in 2005 (2–5) led to significant insights on the pathogenesis of these disorders. In fact, this mutation results in a gain-of-function with activation of cytokine and growth factor receptors, and thus of the downstream JAK-STAT pathway (79, 95–98). The JAK2 point mutation in exon 12, present in a small percentage of patients with PV, is able to induce the MPN phenotype through the same pathogenic mechanism (6, 7). In 2006 the MPLW515L/K was reported in ET and PMF patients (44, 45) and d...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we have shown the safety and efficacy of Vemurafenib in a pediatric patient with DS affected by PXA. Ethics Statement This study was carried out in accordance with the recommendations of the Internal Review Board of the Bambino Gesù Children's Hospital with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Internal Review Board of the Bambino Gesù Children's Hospital. Informed Consent The authors declare that written informed consent was obtained from the pat...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Myelodysplastic Syndromes (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are heterogeneous clonal hematopoietic disorders resulting in inefficient hematopoiesis and a variable progression risk to secondary acute myeloid leukemia (AML).1-3 At diagnosis, the international prognostic scoring system (IPSS)1 and the revised international prognostic scoring system (IPSS-R)2 are commonly used to estimate disease aggressiveness for subsequent therapeutic decision making. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for MDS patients and is of particular intere...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasm (MPN) are heterogeneous clonal hematopoietic disorders resulting in inefficient hematopoiesis and a variable progression risk to secondary acute myeloid leukemia (sAML) [1-3]. At diagnosis, the International Prognostic Scoring System (IPSS) [1] and the revised IPSS (IPSS-R) [2] are commonly used to estimate disease aggressiveness for subsequent therapeutic decision-making. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for MDS patients and is of particular interest in high-risk disease [4].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
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