Single Center Experience with the Use of Hypomethylating Agents in Combination with Donor Lymphocyte Infusions As Initial Salvage Therapy Post Allogeneic Stem Cell Transplant in Relapsed AML/MDS/MPN

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

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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
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
Hematological malignancies can manifest as extramedullary soft tissue masses in relatively rare cases. The rarity of it causes a diagnostic and therapeutic challenge. One of the rarest manifestations is myeloid sarcoma (MS). MS develops as part of acute myeloid leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or at relapse, especially following allogeneic hematopoietic stem cell transplant. The tumor displays high myeloperoxidase expression, hence the color green, and is called chloroma. It most commonly appears in lymph nodes, skin and soft tissues, bone, testes, gastrointestinal tract, and peritoneum. I...
Source: Oncology Research and Treatment - Category: Cancer & Oncology Source Type: research
Conclusions:The current study, the largest coming from a single institution, provides practically useful information that should assist with patient consultation on AML prognosis and treatment. The study confirms the primary prognostic importance of age, karyotype and FLT3/NPM1 mutational status, in real-life practice. Novel observations included comparable value of CRi vs CR and the particularly worse prognosis associated with post-MPN AML.DisclosuresAl-Kali: Novartis: Research Funding.
Source: Blood - Category: Hematology Authors: Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II Source Type: research
ConclusionOur first-in-human clinical trial demonstrates promising efficacy of cCAR therapy in treating patients with relapsed/ refractory AML. cCAR is able to eradicate leukemia blasts and leukemia stem cells, exerting a profound tumor killing effect that is superior to single target CAR T cell therapies. cCAR is also shown to induce total myeloid ablation in bone marrow, suggesting that it may act as a safer alternative to avoid the severe toxicities caused by standard bone marrow ablation regimens without sacrificing the anti-tumor efficacy. This strategy will likely benefit patients who are unable to tolerate total bod...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
In this study, we looked at the presence of this CNVdup14 in a cohort of Caribbean islands patients (pts) with non-secondary aggressive hematological malignancies (HM). We also studied the expression of ATG2B and GSKIP genes in a cohort of acquired AML pts.This is a retrospective multicenter study of adults Caribbean islands pts treated at Gustave Roussy Cancer Center (Villejuif, France) and at the French West Indian hospitals (Martinique and Guadeloupe) between May 2000 and May 2018. We included pts with AML, acute undifferentiated leukemia (AUL), acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Pts wit...
Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research
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