No abstract

The t(14;18) translocation constitutes the initiating event of a causative cascade leading to follicular lymphoma (FL). t(14;18) translocations are present in blood from healthy individuals, but there is a trend of increased prevalence in farmers exposed to pesticides, a group recently associated with higher risk of t(14;18) + non-Hodgkin's lymphoma development. A direct connection between agricultural pesticide use, t(14;18) in blood, and malignant progression, however, has not yet been demonstrated. We followed t(14;18) clonal evolution over 9 yr in a cohort of farmers exposed to pesticides. We show that exposed individuals bear particularly high t(14;18) frequencies in blood because of a dramatic clonal expansion of activated t(14;18) + B cells. We further demonstrate that such t(14;18) + clones recapitulate the hallmark features of developmentally blocked FL cells, with some displaying aberrant activation-induced cytidine deaminase activity linked to malignant progression. Collectively, our data establish that expanded t(14;18) + clones constitute bona fide precursors at various stages of FL development, and provide a molecular connection between agricultural pesticide exposure, t(14;18) frequency in blood, and clonal progression.

The Philadelphia chromosome (Ph+), corresponding to translocation t(9;22), is found in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia. Several cases of Ph+ acute myeloid leukemia (AML) have been reported in the literature. A retrospective study of Ph+ AML between 2001 and 2012 was conducted through a review of the literature. Among 400 AML patients, two cases of Ph+ AML (0.5%) were identified and treated with conventional chemotherapy with or without tyrosine kinase inhibitors (TKIs), followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). One patient had a complex karyotype including 7 monosomy (-7) and p190 BCR-ABL fusion transcript. Both patients remain in complete molecular remission. To date, 21 Ph+ AML cases treated with TKIs have been described in the literature with a median overall survival of 18months. One-third of the patients had additional karyotypic abnormalities, and 14% had -7. Molecular analysis showed 59% p210 and 41% p190 fusion protein. Relapse rate was observed in 38% of patients with p190 compared to 10% in patients with p210. Allo-HSCT was performed in eight patients; two relapsed (25%). Cytogenetic (-7) and molecular features help to distinguish Ph+ AML from CML. Survival improved with TKIs, particularly in association with conventional chemotherapy and allo-HSCT. Further studies of Ph+ AML patients are needed to better define this entity, its prognostic value, and therapeutic strategy.

No abstract

The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO (N  =  61) or MRD (N  =  90) between January 2011 and January 2016. GRFS was defined as the probability of being alive without evidence of relapse, grade 3-4 acute GVHD or chronic GVHD. In multivariable analysis, MRD donors were independently associated with lower GRFS compared to HAPLO donors (HR  =  2.95, P < 0.001). Disease status at transplant other than CR was also associated with lower GRFS in multivariable analysis (HR  =  1.74, P  =  0.01). In addition, the administration of ATG was independently linked to higher GRFS (HR  =  0.52, P  =  0.009). In summary, we observed significantly higher GRFS in HL patients receiving an allo-HCT using the HAPLO PT-Cy platform compared to MRD.