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Although targeted therapies are used increasingly in hematologic malignancies, we are unaware of any prior studies of radioimmunotherapy ( RAIT) in B-acute lymphoblastic leukemia ( ALL), even though this radiosensitive tumor expresses CD22, potentially a good target for this approach. Here, we report a patient with Philadelphia chromosome-positive B- ALL in third relapse who received RAIT with 90yttrium (90 Y)-labeled anti- CD22 epratuzumab tetraxetan. Seven weeks after initiating therapy, the patient achieved a BCR- ABL1 molecular remission documented by RT-q PCR, which is now continuing at 6 months while awaiting an allogeneic hematopoietic stem cell transplant. 90Y-Epratuzumab tetraxetan may be a promising therapeutic option for CD22+ B- ALL patients. [ABSTRACT FROM AUTHOR]

We investigated 16 patients with elevated serum monoclonal IgG and a leukaemic B-cell lymphocytic disorder different from multiple myeloma. Their clinical history was that of a non-aggressive disease with dominant splenomegaly and long survival. Whereas abnormal blood and bone marrow cells were predominantly small lymphocytes with a few lymphoplasmacytoid cells, histopathological features included a lymphoplasmacytic infiltrate in eight cases. Most frequently, abnormal blood cells displayed a CD19+CD5-CD23+/– immunophenotype different from that of chronic lymphocytic leukaemia, except in two cases with a CD19+CD5+CD23+ phenotype. Interestingly, a coexistent serum monoclonal IgM and/or surface IgMG+ with identical light chain was identified in 10 patients, whereas in the remaining six patients only IgG expression was determined. VH gene analysis was performed in eight patients to investigate the clonal origins of tumour cells. All cases utilized the VH3 family, with evidence of extensive somatic mutations and intraclonal homogeneity in all cases. VH gene analysis indicated a clonal relationship between cells expressing IgM and IgG, with one case being biclonal. Cytogenetic evaluation showed a high incidence of trisomy 12 (60%) and 13q14 deletion (40%). In conclusion, we have described an unusual subset of low-grade lymphoma with high-serum IgG and frequent lymphoplasmacytoid features in which tumour cells derive from post-follicular memory B cells undergoing isotype switching with some cases arrested at both the IgM and IgG stage and others as IgG-positive cells only. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning possible treatment for acute myeloid leukemia.

Abstract: No series have reported the results of the use of the therapeutic anti-CD20 monoclonal antibody (Rituximab) in the setting of adult refractory/relapsed B-ALL. We report here the outcomes of such nine patients treated at two french institutions by a combination of Rituximab+chemotherapy. We showed that four patients could achieve complete response while four other patients were documented with blast clearance superior to 50% from the baseline in bone marrow. We conclude that our results suggested some efficacy for the use of Rituximab in combination with chemotherapy in the setting of refractory/relapsed adult B-ALL. Larger series within prospective trials are needed to confirm these results. [Copyright &y& Elsevier]

Abstract: CD117 (c-kit) was evaluated on normal plasma cells (PC) (n =10), PC of individuals with monoclonal gammopathy of undetermined significance (MGUS, n =12), malignant PC from patients with multiple myeloma (MM) either at diagnosis (n =83) or relapse (n =38) and on 23 human myeloma cell lines (HMCL). Whereas CD117 is never expressed in normal PC, it is expressed in 50% of MGUS (p =0.015). Furthermore, 33% of MM at diagnosis do express CD117, as opposed to 8% of those in relapse (p =0.003). Finally, CD117 was never found in HMCL. CD117 expression was associated with a better prognosis: overall survival was 93% at 4 years in CD117+ MM versus 64% in CD117− MM (p =0.05). Conversely, lack of CD117, but also high beta-2 microglobulin, t(4;14) and CD221 (IGF-1R) expression were associated with a poorer prognosis. Multivariate analysis revealed that CD117− patients were those with CD221 and t(4;14) and had the poorest prognosis. In conclusion, CD117 (c-kit) is aberrantly expressed on a subset of MGUS and MM with a more indolent presentation and is functionally antinomic to CD221 (IGF-1R). CD117 expression could be related to a specific oncogenic pathway in MM. [Copyright &y& Elsevier]

The article discusses research that proposed whole blood flow cytometry for the diagnosis of Scott syndrome. Topics covered include the use of flow cytometry in whole blood to detect phosphatidyl serine (PS) on activated platelets' surface, the evaluation of PS flip-flop on platelets in whole blood, and the difficulty of diagnosing primary haemostasis disorders.

Dear Editor, Plasmablastic lymphoma (PBL), according to the WHO classification of tumors, is a very aggressive non-Hodgkin lymphoma characterized by a diffuse proliferation of immunoblastic to plasmacytic large cells in the peripheral blood with a CD20-negative plasmacytic phenotype [[1]]. The patient was addressed in hematology for a suspicion of plasma cell leukemia after detection of 26% circulating plasma cells in a preoperative complete blood count (CBC). Flow cytometry disclosed 8% of nucleated cells expressing CD38, CD138, CD19, CD27, and cytoplasmic light-chain restriction, lacking CD20 and CD22 consistent with plasma cells (Fig. [Extracted from the article]

The article focuses on mutation of ANO6 gene in the cases of Scott syndrome and its diagnosis relies on flow cytometry and molecular diagnosis. It mentions exposure of phosphatidylserine (PS) on the outer leaflet of the platelet membrane and a severe decrease in the production of microparticles (PMP) after platelet activation. It also mentions haemostasis exploration was normal except for increased residual serum prothrombin.

The article describes the case of a 31-year-old man presented with acute respiratory distress, fatigue and persistent fever and diagnosed with lymphoma associated with human herpes virus 8 (HHV8). Topics discussed include the patient's history cutaneous and pulmonary Kaposi sarcoma and human immunodeficiency virus (HIV) infection, partial expression of CD19 shown on flow cytometry and importance of immunophenotyping in determining the abnormal cells and establishing a definitive diagnosis.

The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (<10 -6 ). Data were analyzed from a recent clinical trial that evaluated the role of transplantation in newly diagnosed myeloma patients treated with lenalidomide, bortezomib, and dexamethasone (RVD). MRD negativity was achieved at least once during maintenance in 127 patients (25%). At the start of maintenance therapy, MRD was a strong prognostic factor for both progression-free survival (adjusted hazard ratio, 0.22; 95% confidence interval, 0.15-0.34; P < .001) and overall survival (adjusted hazard ratio, 0.24; 95% confidence interval, 0.11-0.54; P = .001). Patients who were MRD negative had a higher probability of prolonged progression-free survival than patients with detectable residual disease, regardless of treatment group (RVD vs transplant), cytogenetic risk profile, or International Staging System disease stage at diagnosis. These results were similar after completion of maintenance therapy. Our findings confirm the value of MRD status, as determined by NGS, as a prognostic biomarker in multiple myeloma, and suggest that this approach could be used to adapt treatment strategies in future clinical trials., (© 2018 by The American Society of Hematology.)

Background: Prognosis of patients with relapsed or refractory acute lymphoblastic leukaemia is poor and new treatments are needed. We aimed to assess the feasibility, tolerability, dosimetry, and efficacy of yttrium-90-labelled anti-CD22 epratuzumab tetraxetan ((90)Y-DOTA-epratuzumab) radioimmunotherapy in refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia in a standard 3 + 3 phase 1 study., Methods: Adults (≥18 years) with relapsed or refractory B-cell acute lymphoblastic leukaemia (with CD22 expression on at least 70% of blast cells) were enrolled at six centres in France. Patients received one cycle of (90)Y-DOTA-epratuzumab on days 1 and 8 (give or take 2 days) successively at one of four dose levels: 2·5 mCi/m(2) (92·5 MBq/m(2); level 1), 5·0 mCi/m(2) (185 MBq/m(2); level 2), 7·5 mCi/m(2) (277·5 MBq/m(2); level 3), and 10·0 mCi/m(2) (370 MBq/m(2); level 4). The primary objective was to identify the maximum tolerated dose of (90)Y-DOTA-epratuzumab. We assessed safety during infusions and regularly after radioimmunotherapy over a 6-month period. Analyses included only patients who received radioimmunotherapy. The trial is closed to inclusion and is registered at ClinicalTrials.gov, NCT01354457., Findings: Between Aug 25, 2011, and June 11, 2014, 17 patients (median age 62 years; range 27-77) were treated (five at level 1, three at level 2, three at level 3, and six at level 4). Radioimmunotherapy infusion was overall well tolerated. One dose-limiting toxic effect (aplasia lasting 8 weeks) occurred at level 4, but the maximum tolerated dose was not reached. The most common grade 3-4 adverse events were pancytopenia (one patient at level 2, one at level 3, and six at level 4) and infections (three at level 1, one at level 2, and five at level 4)., Interpretation: (90)Y-DOTA-epratuzumab radioimmunotherapy is well tolerated. We recommend the dose of 2 × 10·0 mCi/m(2) 1 week apart per cycle for phase 2 studies., Funding: Immunomedics and Direction de la Recherche Clinique of Nantes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Cord Blood (CB) are increasingly used as an alternative stem cells source in adults for allogeneic Stem Cell Transplantation (allo-SCT). The risk of human herpesvirus (HHV-6) reactivation is significantly higher after CB transplant vs unrelated peripheral blood stem cells (PBSC) allo-SCT. Higher HHV-6 cell receptor CD46 expression on progenitor cells in CB may explain this difference., Objectives: To prospectively compare the HHV-6 cell receptor CD46 expression on various cell subsets of three freshly harvested blood sources on one hand and of three graft sources on the other hand., Study Design: 52 samples were used for the purpose of this study. They were issued from peripheral blood (PB, n = 10), G-CSF mobilised PB (GCSF-PB, n = 10), cord blood (CB, n = 10), unmanipulated bone marrow (uBM, n = 5), leukapheresis product (LP, n = 10) and thawed CB graft (n = 7). CD46 expression was assessed by FACS analysis on total lymphocytes, monocytes, NK cells, T and B cells subsets, plasmacytoid (pDCs) dendritic cells and stem cells., Results: As all cell subsets were found CD46 positive, CD46 mean fluorescence intensity (MFI) was then considered for comparison between the three blood sources and the three graft sources. The most impressive result observed was that HHV-6 cell receptor CD46 expression was significantly reduced in almost all cell components of thawed CB graft compared to other graft sources., Conclusions: This original study shows strong differences in term of quantitative CD46 expression between several blood and grafts samples. Our results suggest that other factors than the qualitative CD46 expression play a role in the higher HHV-6 reactivation observed after CB transplant in adults., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Human memory T cells are comprised of distinct populations with different homing potential and effector functions: central memory T cells that mount recall responses to Ags in secondary lymphoid organs, and effector memory T cells that confer immediate protection in peripheral tissues. In the present study we demonstrate that a proportion of effector memory T cells express FcgammaRIIIa (CD16), are perforin positive, and directly mediate Ab-dependent cytotoxicity ex vivo. This particular alphabeta T lymphocyte subset has the morphology of large granular lymphocytes, increases proportionately in vivo during reactive lymphocytosis, and can be detected in vitro among EBV-specific T lymphocytes after stimulation with EBV Ags. Consequently, during a normal immune response, amplification of these effector memory T lymphocytes that are capable of Ab-dependent cytotoxicity may have beneficial or harmful consequences depending on the presence of pathogen- or tissue-specific Abs, respectively.

The aim of this review is to integrate non-exhaustive relevant data on the phenotype of human plasma cells (PC), including normal, reactive and malignant (multiple myeloma, MM) PC. This review focuses on (i) a universal marker of both normal and malignant plasma cells, CD138; (ii) markers related to malignancy i.e., CD19, CD27, CD28, and CD56; (iii) markers associated with signaling and severity of MM (CD45, CD221). Finally, this review presents data from normal PC up to human myeloma cell lines in order to: (i) define different entities of MM based on expression of CD19, CD20, CD27 and CD117; and (ii) identify new therapeutic targets.

Background and Objectives: Competitive immunoglobulin/T-cell receptor polymerase-chain reaction (PCR) analysis with fluorescent detection is a rapid, cheap and reproducible method for quantifying minimal residual disease (MRD), which is well adapted to the recognition of high-risk childhood acute lymphoblastic leukemia (ALL). We aimed at defining whether flow cytometry (FC) techniques can bypass limitations of PCR for MRD determination., Design and Methods: We analyzed 140 remission samples from 91 patients using both competitive PCR amplification of antigen-receptor genes and four-color FC identification of leukemia immunophenotype. These methods were chosen with the aim of detecting at least 0.1% blasts., Results: MRD was measured using both PCR and FC methods in 123 samples and the two methods provided concordant results in 119 of them (97%). Moreover, three out of the four discordant results appeared minor since MRD was detectable by both methods, but at different levels. In 12 of 13 samples from nine patients, mainly infants with early CD10- and/or t(4;11) B-cell ALL and children with immature T-cell ALL, MRD could be determined using FC whereas PCR failed. Conversely, FC methods were unfeasible due to inappropriate leukemia immunophenotype in three additional children (including two with T-cell ALL) for whom PCR successfully provided MRD results., Interpretation and Conclusions: The MRD results provided by FC techniques were highly concordant with those of competitive PCR. Moreover, the applicability of FC appeared higher in certain ALL subsets, although the appropriateness of this technique in terms of outcome prediction remains to be demonstrated.

It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4(+)CD25(+) T cell compartment. Here, we describe an original method to purify human CD4(+)CD25(+)CD152(+) T lymphocytes as living cells by forcing the exportation of CTLA-4 molecules stored in intracellular vesicules at the cell surface. By doing so, we demonstrate that CD4(+)CD25(+) T cells contain a smaller and more homogeneous population enriched in cells with in vitro regulatory activity. Moreover, we show that this enrichment in regulatory T cells is associated with an increased expression of Foxp3 and that CD4(+)CD25(+)CD152(+) T lymphocytes display a much stronger suppressive activity in controlling in vitro proliferation of alloantigen-specific T cells than CD4(+)CD25(+)CD152(-) T lymphocytes purified in parallel. Lastly, by purifying such cells expressing CTLA-4, we demonstrate that indeed CTLA-4 is involved in CD4(+)CD25(+)CD152(+) T cell regulatory activity, while suppressive cytokines are not.

Background and Objectives: CD45 is a critical regulator of signaling threshold in immune cells. There are clinical and animal studies suggesting that the CD45-negative phenotype is the phenotype of progressive multiple myeloma (MM). The aims of this study were to confirm this hypothesis and to test the prognostic value of CD45 expression in newly diagnosed MM patients., Design and Methods: In a retrospective study of 95 newly diagnosed MM patients treated with high dose therapy we used 4-color flow cytometry to determine CD45 expression and correlated the immunophenotipic data with clinical data., Results: Thirty of 95 patients (31.5%) lacked CD45 expression at diagnosis. The CD45 phenotype significantly affected the overall survival (OS) of the patients, like the most common presenting prognostic parameters analyzed including b-2-microglobulin, age and 14q32 translocations. CD45 negative MM patients had a significantly worse OS than did CD45 positive cases of MM: 28.7% cumulative survival at 4 years, median 42 months vs not reached; p = 0.004. Furthermore, CD45 remained the only parameter adversely affecting OS in multivariate analysis., Interpretation and Conclusions: The CD45 negative phenotype could reflect the phenotype of progressive disease in relation to the intrinsic malignancy of the MM clone. Indeed, CD45 negative myeloma cells appear to have a greater capacity to circulate, disseminate and clone as well as being less sensitive to apoptosis.