Alpha/Beta T-Cell and B-Cell Depletion HLA-Haploidentical Hematopoietic Stem Cell Transplantation Is an Effective Treatment for Children/Young Adults with Acute Leukemia

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children/young adults with acute leukemia (AL) either relapsed or at high-risk of treatment failure and in urgent need of an allograft. A novel method of graft manipulation based on the selective, negative depletion of αβ T and B cells has been recently developed. We published the results of a prospective trial (ClinicalTrial.gov identifier: NCT01810120) enrolling 80 children with AL transplanted until September/2014 using this approach (Locatelli, Blood 2017). In the present analysis, we update those results, evaluating also additional patients given haplo-HSCT after that date.Patients and methods: Analyzed are 111 children with AL enrolled in the trial; median age is 10 years (range 0.9-22.2). Eighty-two (74%) and 29 (26%) patients had acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), respectively; they were transplanted between 09/2011 and 05/2018. All children were transplanted in complete morphological remission and received a fully myeloablative preparative regimen. Details on patients' characteristics, as well as on the number of HSC and lymphocyte subsets infused, are shown in Table 1. The donor was mainly chosen according to immunological criteria, giving priority to NK-cell alloreactivity, evaluated according to the killer immunoglobulin-like receptor (KIR)/KIR-Ligand mismatch in graft-versus-hos...
Source: Blood - Category: Hematology Authors: Tags: 732. Clinical Allogeneic Transplantation: Results: Poster I Source Type: research

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Authors: Winters A, Gore L Abstract Although almost 90% of children with acute lymphoblastic leukemia (ALL) and ∼60% of children with acute myeloid leukemia are cured with frontline therapy, relapse and chemotherapy resistance are significant challenges that contribute to morbidity and mortality. Even with long-term survival, the acute and chronic burdens of therapy are major issues for patients and families. Long-term side effects occur, including cardiac, endocrinologic, neurcognitive, orthopedic, and psychosocial problems, and healthy survivorship is frequently compromised. With goals of minimizing relapse a...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Keserű Richard Moriggl Signal transducer and activator of transcription (STAT)3 and STAT5 are important transcription factors that are able to mediate or even drive cancer progression through hyperactivation or gain-of-function mutations. Mutated STAT3 is mainly associated with large granular lymphocytic T-cell leukemia, whereas mutated STAT5B is associated with T-cell prolymphocytic leukemia, T-cell acute lymphoblastic leukemia and γδ T-cell-derived lymphomas. Hyperactive STAT3 and STAT5 are also implicated in various hematopoietic and solid malignancies, such as chronic and acute myeloid leukem...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ConclusionWe suggest a one ‐compartment population model with first‐order elimination to capture the pharmacokinetic profile for basiliximab for this patient population.
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research
Abstract Our objective was to determine the association between the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) and the risk of developing acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and multiple myelomas (MM) in Latinos. PubMed, SCOPUS, EBSCO, LILACS, and other Latin-specific databases were searched for case-control studies that investigated the association between these polymorphisms and hematologic malignancies until November 2017. Genotype distributions were extracted and either fixed-effects or random-effects models were used to calculate t...
Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research
Conclusion: The cumulative incidence of malnutrition in Finnish pediatric cancer patients is comparable to that reported in other populations. The nutritional status of patients with acute myeloid leukemia, CNS tumors, or solid tumors should be monitored with extra care to facilitate early intervention in the case of impending malnutrition.What is known:•Both malnutrition and obesity are associated with reduced survival and increased drug toxicity in pediatric cancer patients.What is new:•Overall, 28 % of Finnish children receiving chemotherapy for cancer suffer from malnutrition during the first 42 months follow...
Source: European Journal of Pediatrics - Category: Pediatrics Source Type: research
Platzbecker The ability to detect residual levels of leukemic blasts (measurable residual disease, MRD) has already been integrated in the daily routine for treatment of patients with chronic myeloid and acute lymphoblastic leukemia. In acute myeloid leukemia (AML), a variety of mostly retrospective studies have shown that individuals in AML remission who tested positive for MRD at specific time-points or had increasing MRD levels are at significantly higher risk of relapse and death compared to MRD-negative patients. However, these studies differ with respect to the “MRD-target”, time-point of MRD ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Abstract Recent genetic analysis using next-generation sequencing (NGS) vastly improved the understanding of molecular mechanism of hematological malignancies. Many molecular targeting drugs have since been used in the clinic, which is timely as clinical outcomes using conventional chemotherapy and hematopoietic stem cell transplantation (HSCT) reached a plateau. The first memorable success in this field was imatinib, a first-generation tyrosine kinase inhibitor (TKI), which has been applied in chronic myeloid leukemia (CML) since 2001. Imatinib drastically changed CML treatment and many CML patients no longer req...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Auer rods were first described in the cytoplasm of leukemia blasts by John Auer in 1906. Auer rods are commonly seen in myeloid progenitors, and serve as a diagnostic morphological feature of acute myeloid leukemia (AML) [1]. The differential diagnosis of hematopoietic neoplasms relies on the detection of cytoplasmic inclusions resembling Auer rods. Auer rod-like inclusions have been described in multiple myeloma [2], prolymphocytic leukemia (PLL) [3], B-cell acute lymphoblastic leukemia [4], chronic lymphocytic leukemia [4], splenic lymphoma [5] and nodal marginal zone lymphoma [6], which are quite distinct from the needl...
Source: Experimental Hematology - Category: Hematology Authors: Tags: Brief Communication Source Type: research
The interaction of natural killer (NK) cell inhibitory receptors with polymorphic HLA class I molecules educates NK cells for immune surveillance against tumor cells. The KIR A haplotype, which encodes distinct NK cell inhibitory receptors that bind certain HLA-A, -B and -C allotypes, is unusually frequent in East Asians. Focusing on Chinese southern Han, we analyzed 472 acute lymphoblastic leukemia (ALL), 433 acute myeloid leukemia (AML), 193 chronic myeloid leukemia (CML) patients, and 745 healthy controls. We observed a higher frequency of KIR A homozygosity in the healthy controls than in all the leukemia patients comb...
Source: Frontiers in Immunology - Category: Allergy & Immunology 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
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