Clonal Hematopoiesis and Bone Marrow Infiltration in Patients With Follicular Helper T-Cell Lymphoma of Angioimmunoblastic Type.

Follicular helper T-cell (TFH) lymphoma harbors recurrent mutations of RHOAG17V, IDH2R172, TET2, and DNMT3A. TET2 and DNMT3A mutations are the most frequently affected genes in clonal hematopoiesis (CH). The aim of our study was to investigate the frequency of CH in bone marrow biopsies (BMB) of TFH/angioimmunoblastic T-cell lymphoma (TFH-AITL) patients and its association with myeloid neoplasms. A total of 29 BMB from 22 patients with a diagnosis of TFH-AITL were analyzed by next-generation sequencing (NGS) with a custom panel. Morphologically, 5 BMB revealed that TFH-AITL infiltrates of >5% of bone marrow (BM) cellularity confirmed in 4 cases by NGS-based T-cell clonality. IDH2R172 was demonstrated only in 1 (3%) of 29, and RHOAG17V in 2 (7%) of 29 samples. TET2 and DNMT3A were identified in 24 (83%) of 29 and 17 (59%) of 29 BMB, respectively. In the parallel lymph node the frequencies of mutations were 27% (IDH2R172), 64% (RHOAG17V), 86% (TET2), and 50% (DNMT3A). TET2 and/or DNMT3A mutations identical in lymph node and BMB were present in 18 (82%) of 22 patients, regardless of BM infiltration. In 3 cases the CH mutations were detected 13, 41, and 145 months before TFH-AITL diagnosis. Cases with TET2/DNMT3A mutations and BM variant allele frequencies >40% (7/18, 39%) showed lower blood counts. However, only low platelet count was statistically significant (P = .024). Myeloid neoplasms and/or myelodysplastic syndrome-related mutations were identified in 4 cases (4/22; 18%); all with high TET2 variant allele frequencies (>40%; P = .0114). In conclusion, CH is present in 82% of TFH-AITL and can be demonstrated up to 145 months before TFH-AITL diagnosis. NGS T-cell clonality analysis is an excellent tool to confirm TFH-AITL BM infiltration. Concurrent myeloid neoplasms were identified in 18% of the cases and were associated with TET2 mutations with high allelic burden (>40%). We demonstrated that myeloid neoplasms might occur simultaneously or precede the diagnosis of TFH lymphoma.

Real-world evidence on tagraxofusp for blastic plasmacytoid dendritic cell neoplasm - collected cases from a single center and case reports.

Introduction: Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare, aggressive hematologic malignancy. Until recently, the only curative treatment consisted of intensive chemotherapy, followed by hematopoietic cell transplantation (HCT) in eligible adult cases. Tagraxofusp, a CD123-targeted protein-drug conjugate and the first approved targeted treatment for BPDCN, might enhance outcomes especially in patients not eligible for intensive therapies. Methods: Here, we report real-world outcomes of five male patients with a median age of 79 years who received tagraxofusp as first-line treatment for BPDCN. Results: Tagraxofusp was found to be well-tolerated in this elderly cohort, with only one patient requiring discontinuation. Three patients responded to the treatment (two patients achieved a CR and one patient achieved a partial response), of which two subsequently underwent allogeneic (allo) HCT. One patient is alive and well after ≥ 4 years after alloHCT, and one patient shows sustained CR after now 13 cycles of tagraxofusp. The other three patients died of progressive disease 4-11 months after initiation of treatment. Discussion: In line with results from 13 published cases outside clinical trials in the literature, sustained responses were associated with CR after tagraxofusp treatment and subsequent alloHCT. Our results provide real-world evidence for safety and efficacy of tagraxofusp as first-line treatment for BPDCN.

Clonal haematopoiesis: A common progenitor for cytotoxic peripheral T-cell lymphoma and angioimmunoblastic T-cell lymphoma.

Recent studies have shown that follicular helper T-cell lymphoma of angioimmunoblastic type (AITL), the most common nodal peripheral T-cell lymphoma (PTCL), frequently arises in a background of clonal haematopoiesis (CH), a preneoplastic condition affecting up to 40% of elderly individuals. Data on a potential CH association are limited for other PTCL. We report a unique patient who sequentially developed both cytotoxic PTCL, not otherwise specified and AITL with distinct T-cell receptor rearrangements but shared somatic mutations originating from the same CH clone, thus providing convincing evidence that CH can give rise to T-cell neoplasms of different lineage.