Clinical Response to Upfront Targeted Tyrosine Kinase Inhibitors among Patients with Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Gene Fusion.

INTRODUCTION: Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion (MLN-TK) is an entity encompassed of a heterogeneous group of rare hematopoietic neoplasms that are driven by gene fusion involving PDGDRA/B, FGFR1, JAK2, FLT3 or ETV6::ABL1. Though patients presenting with chronic phase MLN-TK with PDGFRA fusion display a favorable outcome in response to upfront TK inhibitor (TKI) therapy, the outcomes of MLNs driven by other TK fusions are not well described. In this study, we aimed to critically analyze the treatment outcomes of patients with MLN-TK, focusing on the role of upfront TKIs in both chronic- and blast-phase diseases. METHODS: The retrospective study included patients with confirmed MLN-TK from 3 centers and assessed demographic and clinical variables, treatment, and outcomes. RESULTS: Forty-two patients with confirmed MLN-TK [PDGFRA (n = 22), PDGFRB (n = 4), FGFR1(n = 10), JAK2 (n = 2); and FLT3 (n = 3)] were included. Fifteen of 25 (60%) chronic-phased patients received upfront TKI therapy had a long-term remission. Nine of 16 (60%) blast-phase patients with upfront TKIs also achieved complete remission and remained alive at a median follow-up of 20 months. All 3 patients with blast phase disease who received upfront chemotherapy without positive response did not respond to subsequent TKI therapy, emphasizing the importance of initiating TKI therapy early. Upfront TKI therapy was associated with longer overall survival in univariate analyses (HR, 0.054 [95% CI, 0.007-0.42]) and multivariate analyses (HR, 0.03 [95% CI, 0.002-0.47]). CONCLUSION: The outcomes of upfront TKI therapy are excellent for MLN-TK in both chronic and blast phases, regardless of gene abnormalities.

Distinct pathologic feature of myeloid neoplasm with t(v;11p15); NUP98 rearrangement.

Chromosome rearrangements involving NUP98 at 11p15 are rare but recurring abnormalities in acute myeloid leukemia (AML). Here we described 12 cases of myeloid neoplasms with t(v; 11p15); NUP98 rearrangement and characterized their pathologic features. Our patient cohort included 10 adults and 2 children with a median age of 51 years. They were predominantly AML (n = 10) including de novo AML, therapy-related AML, chronic myeloid leukemia with myeloid blast crisis, and mixed phenotype acute leukemia, as well as therapy-related myelodysplastic syndrome (MDS) and MDS/myeloproliferative neoplasm with increased blasts. The blasts shared some common features including pink/red cytoplasmic granules, presence of a perinuclear hof, Auer rods, and occasional bilobed nuclei, mimicking acute promyelocytic leukemia (APML). Flow cytometric studies showed blasts positive for MPO, CD117, CD13 and CD33, with a subset of cases negative for CD34 and/or HLA-DR and a subset of cases expressing monocytic markers. The translocations of 11p15 included t(7; 11) (p15; p15), t(2; 11) (q31; p15), t(9; 11) (p22; p15), t(5; 11) (q32; p15), and t(11; 12) (p15; q13). Three cases showed cryptic NUP98 rearrangement. These patients showed incomplete response to therapy with median overall survival of 17.5 months, a complete remission rate of 25% following chemotherapy induction and primary refractory disease of 58%. It is clinically important to recognize this group of diseases because the blasts can be misclassified as promyelocytes, and NUP98 rearrangement may be cryptic requiring fluorescence in situ hybridization (FISH) study. This case series highlights that NUP98-rearranged myeloid neoplasms are clinically, morphologically, and cytogenetically distinct and could be considered as a separate entity in the WHO classification defined by cytogenetic abnormality.

Primary Central Nervous System Lymphomas: A Diagnostic Overview of Key Histomorphologic, Immunophenotypic, and Genetic Features.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that primarily arises in the brain, spinal cord, leptomeninges, and vitreoretinal compartment of the eye. The term is sometimes used interchangeably with primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) because DLBCL comprises a great majority (90-95%) of PCNSL. Although rare, other types of lymphomas can be seen in the central nervous system (CNS), and familiarity with these entities will help their recognition and further workup in order to establish the diagnosis. The latter is especially important in the case of PCNSL where procurement of diagnostic specimen is often challenging and yields scant tissue. In this review, we will discuss the most common types of primary lymphomas that can be seen in the CNS with emphasis on the diagnostic histomorphologic, immunophenotypic, and molecular genetic features. The differential diagnostic approach to these cases and potential pitfalls will also be discussed.

Capsular synovial metaplasia mimicking radiographic features of implant-associated anaplastic lymphoma.

Delayed onset breast implant-associated reactions range widely in symptomatology and underlying etiology. With increasing reports of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), findings such as unilateral breast swelling, capsular thickening, and peri-implant fluid raise concern. Synovial metaplasia is a benign histologic finding commonly associated with implant capsules and can be an unusual cause of such symptoms. Though the clinical significance of synovial metaplasia is unknown, it is important to consider this entity in the differential diagnosis for delayed onset breast symptoms, with signs otherwise concerning for BIA-ALCL or infection.

Preliminary findings on the use of pulsatile machine reperfusion of a placenta to improve the cord blood collection yield including primitive hematopoietic stem cell fractions.

BACKGROUND: Umbilical cord blood (CB) use is limited in most adults since the mean amount of hematopoietic stem cells (HSCs) collected is generally insufficient to engraft successfully. This study demonstrates for the first time the feasibility of pulsatile machine placenta reperfusion (PMPR), which significantly improves CB collection quantity and quality compared to standard collection methods. STUDY DESIGN AND METHODS: PMPR was performed on eight delivered placentas up to 39 hours after venipuncture-based collection. PMPR was performed on average for 26 (20-30) minutes, 17 hours after delivery (6.25-39), using perfusate approved for donated organ reperfusion. Both PMPR and conventional collection-derived CB cells were analyzed using immunophenotyping and colony assays. RESULTS: The combination of PMPR and the conventional venipuncture method yielded a mean of 1.5-, 4.9-, 11-, 7.5-, 7.5-, and 7.7-fold increased number of total mononuclear, CD34+, CD34+/CD38-, CD133+, CD133+/CD34+, and CD133+/CD34- cells, respectively, compared to conventional venipuncture alone. CB cells obtained by PMPR alone generally demonstrated a significant increase in percentages of primitive HSC phenotype with equivalent cell viability between PMPR and venipuncture. CONCLUSION: This article demonstrates for the first time that CB can be collected up to 39 hours after delivery with PMPR while maximizing CB collection including HSCs with primitive phenotypes.